Can serum biomarkers be used to rule out significant intracranial pathology in emergency department patients with mild traumatic brain injury? A Systemic Review & Meta-Analysis

Abstract

Background: Interest has mounted into the use of objective clinical biomarkers for traumatic brain injury (TBI). This systematic review and meta-analysis aimed to synthesise the existing evidence investigating the use of serum & plasma biomarkers to exclude significant intracranial injuries seen on CT head scans in patients that present to ED with TBI.

Methods: The primary outcome was to review the diagnostic accuracy (sensitivity & specificity) of S100B, GFAP and UCH-L1 to exclude significant intracranial pathology on CT head scan in adults presenting with TBI. Secondary outcomes investigated biomarker performance at different time points, in isolated TBI and multi-trauma and with pre-specified cut offs. Systematic searches were conducted on MEDLINE ® (via PubMed), Cochrane electronic databases and EMBASE from 1^st January 2000 until June 2020. Bias was assessed using QUADAS 2 tool. A narrative synthesis and meta-analysis were performed. PROSPERO registration number CRD42020212206.

Results: After screening, 22 papers were included. The total number of patients with TBI was 9,416. There was significant variation regarding study design, population selection and the clinical threshold/decision rule for CT head request. The diagnostic accuracy of S100B as measured by the range of individual sensitivities and specificities were 63-100% and 5-58%, respectively. Individual sensitivities and specificities for GFAP were 67-100% and 0-89% and for UCH-L1 were 61-100% and 21-63.7% respectively. When measured within 3 hours individual sensitivities & specificities for S100B were 98-100% & 20-58% respectively. The quality of evidence for the primary outcome overall was low. The quality of evidence was low for all secondary outcomes apart from studies that used a pre-specified cut off for S100B which had a moderate strength of evidence.

Conclusion: The overall quality of evidence regarding the diagnostic accuracy of single biomarkers as a rule out for significant intracranial injury seen on CT head scans in ED patients with TBI is low. Based on current evidence, S100B is the only single biomarker with a validated clinical platform, pre-determined cut off threshold and moderate quality evidence; at this stage making it the biomarker of choice. More robust clinical outcome and economic impact data is required to support its incorporation into clinical decision tools.

Keywords: CT head; Clinical biomarkers; Emergency department management; GFAP; S100B; Traumatic brain injury; UCH-L1.