Abstract

Objectives To determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury.

Design Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews.

Study selection Two reviewers independently reviewed citations and selected eligible studies, defined as cohort studies or randomised control trials including patients with moderate or severe traumatic brain injury and evaluating the prognostic value of S-100β protein. Outcomes evaluated were mortality, score on the Glasgow outcome scale, or brain death.

Data extraction Two independent reviewers extracted data using a standardised form and evaluated the methodological quality of included studies. Pooled results were presented with geometric means ratios and analysed with random effect models. Prespecified sensitivity analyses were performed to explain heterogeneity.

Results The search strategy yielded 9228 citations. Two randomised controlled trials and 39 cohort studies were considered eligible (1862 patients). Most studies (n=23) considered Glasgow outcome score ≤3 as an unfavourable outcome. All studies reported at least one measurement of S-100β within 24 hours after traumatic brain injury. There was a significant positive association between S-100β protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I²=56%) and score ≤3 (18 studies: 2.62, 2.01 to 3.42, I²=79%). Sensitivity analysis based on sampling time, sampling type, blinding of outcome assessors, and timing of outcome assessment yielded similar results. Thresholds for serum S-100β protein values with 100% specificity ranged from 1.38 to 10.50 µg/L for mortality (six studies) and from 2.16 to 14.00 µg/L for unfavourable neurological prognosis as defined by the Glasgow outcome score.

Conclusions After moderate or severe traumatic brain injury, serum S-100β protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100β protein could be useful in evaluating the severity of traumatic brain injury and in the determination of long term prognosis in patients with moderate and severe injury.

What is already known on this topic

• Many indicators have been independently associated with prognosis after traumatic brain injury, but they are of limited clinical use when considered separately and current prognostic models do not have sufficient discriminative capacity to inform clinical decision making
• S-100β protein concentrations have been shown to increase in blood and cerebrospinal fluid after a wide range of diseases or conditions leading to brain damage
• S-100β protein serum concentrations correlate significantly with unfavourable prognosis in patients with moderate or severe traumatic brain injury, as defined by mortality, Glasgow outcome score ≤3, or brain stem death, with or without concomitant traumatic injuries
• The association between serum concentrations of S-100β protein and prognosis was observed at discharge from intensive care and at one, three, and six months.
• Serum threshold values ranging from 1.38 µg/L to 10.50 µg/L and from 2.16 µg/L to 14.00 µg/L were associated with 100% specificity for mortality and a Glasgow outcome score ≤3, respectively.
• • Source: BMJ

What this study adds