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Use of Serum Biomarkers to Predict Secondary Insults Following Severe Traumatic Brain Injury

ABSTRACT The management of severe traumatic brain injury (TBI) focuses on prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). Predicting which patients will develop these secondary insults is currently not possible. This study investigates the systemic manifestation of neuroinflammation and its role in helping to predict clinical deterioration following severe TBI. Patients with head Abbreviated Injury Severity greater than 3, age older than 14 years, “isolated” TBI, and placement of intracranial pressure monitor were prospectively enrolled. Serum was collected within 24 h and twice daily for 7 days. Measures of moderate and severe ICH (intracranial pressure >20 and >30 mmHg) and moderate and severe CH (cerebral perfusion pressure <60 and <50 mmHg) were compared with interleukin 8 (IL-8) and tumor necrosis factor &agr; (TNF-&agr;) levels drawn before periods of monitoring. An adjusted mixed-model analysis accounting for longitudinal correlations was applied. Sixty-eight patients were enrolled; 670 12-h periods of monitoring and 845 serum samples were available for analysis. Associations were found between serum levels of IL-8 and moderate and severe CH. Levels of TNF-&agr; and severe ICH and CH were also correlated. Specificities of 81% to 95% were found for prediction of ICH and CH for TNF-&agr; and CH for IL-8. Interleukin 8 and TNF-&agr; demonstrate promise as candidate serum markers of impending ICH and CH. This suggests that we may be able to “predict” imminent events following TBI before clinical manifestations. Given the morbidity of ICH and CH, minimizing the effects of these secondary insults may have a significant impact on outcome and help guide decisions about timing of interventions.