Prognostic Value of Glial Fibrillary Acidic Protein in Patients With Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVES: Biomarkers have been suggested as potential prognostic predictors following a moderate or severe traumatic brain injury but their prognostic accuracy is still uncertain. The objective of this systematic review is to assess the ability of the glial fibrillary acidic protein to predict prognosis in patients with moderate or severe traumatic brain injury. DATA SOURCES: MEDLINE, Embase, CENTRAL, and BIOSIS electronic databases and conference abstracts, bibliographies of selected studies, and narrative reviews were searched. STUDY SELECTION: Pairs of reviewers identified eligible studies. Cohort studies including greater than or equal to four patients with moderate or severe traumatic brain injury and reporting glial fibrillary acidic protein levels according to the outcomes of interest, namely Glasgow Outcome Scale or Extended Glasgow Outcome Scale, and mortality, were eligible. DATA EXTRACTION: Pairs of reviewers independently extracted data from the selected studies using a standardized case report form. Mean levels were log-transformed, and their differences were pooled with random effect models. Results are presented as geometric mean ratios. Methodologic quality, risk of bias, and applicability concerns of the included studies were assessed. DATA SYNTHESIS: Seven-thousand seven-hundred sixty-five citations were retrieved of which 15 studies were included in the systematic review (n = 1,070), and nine were included in the meta-analysis (n = 701). We found significant associations between glial fibrillary acidic protein serum levels and Glasgow Outcome Scale score less than or equal to 3 or Extended Glasgow Outcome Scale score less than or equal to 4 (six studies: geometric mean ratio 4.98 [95% CI, 2.19-11.13]; I = 94%) and between mortality (seven studies: geometric mean ratio 8.13 [95% CI, 3.89-17.00]; I = 99%). CONCLUSIONS: Serum glial fibrillary acidic protein levels were significantly higher in patients with an unfavorable prognosis. Glial fibrillary acidic protein has a potential for clinical bedside use in helping for prognostic assessment. Further research should focus on multimodal approaches including tissue biomarkers for prognostic evaluation in critically ill patients with traumatic brain injury.

Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury. METHODS: We searched MEDLINE, Embase, The Cochrane Library and Biosis Previews, and reviewed reference lists of eligible articles to identify studies. We included cohort studies and randomized controlled trials that evaluated the prognostic value of neuron-specific enolase to predict mortality or Glasgow Outcome Scale score in patients with moderate or severe traumatic brain injury. Two reviewers independently collected data. The pooled mean differences were analyzed using random-effects models. We assessed risk of bias using a customized Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Subgroup and sensitivity analyses were performed based on a priori hypotheses. RESULTS: We screened 5026 citations from which 30 studies (involving 1321 participants) met our eligibility criteria. We found a significant positive association between neuron-specific enolase serum levels and mortality (10 studies, n = 474; mean difference [MD] 18.46 µg/L, 95% confidence interval [CI] 10.81 to 26.11 µg/L; I2 = 83%) and a Glasgow Outcome Scale ≤ 3 (14 studies, n = 603; MD 17.25 µg/L, 95% CI 11.42 to 23.07 µg/L; I2 = 82%). We were unable to determine a clinical threshold value using the available patient data. INTERPRETATION: In patients with moderate or severe traumatic brain injury, increased neuron-specific enolase serum levels are associated with unfavourable outcomes. The optimal neuron-specific enolase threshold value to predict unfavourable prognosis remains unknown and clinical decision-making is currently not recommended until additional studies are made available.

Ruptured aneurysmal subarachnoid hemorrhage in the emergency department: Clinical outcome of patients having a lumbar puncture for red blood cell count, visual and spectrophotometric xanthochromia after a negative computed tomography.

OBJECTIVES: Over the last decade, computed tomography scanners have gained resolution and have become the standard of care in the investigation of neurologically intact patients suffering from acute headache. The added value of the combined assessment of red blood cells count, visual and spectrophotometric xanthochromia, to detect ruptured aneurysmal subarachnoid hemorrhage (ASAH) following a negative head computed tomography (NHCT) was studied. METHODS: The population consisted of all patients who had cerebrospinal fluid tested for spectrophotometric xanthochromia between 2003 and 2009 identified through the clinical-laboratory database and who met all the inclusion criteria: >14 years old, had an initial Glasgow Coma Score of 15, a non-traumatic acute headache with a suspected subarachnoid hemorrhage recorded in the initial ED differential diagnosis and an initial negative head CT scan. RESULTS: A total of 706 patients were included. LP identified 5 ASAH (prevalence: 0.7%). In these patients, LP parameters were as follows: high red blood cell count (from 1310 to 63,000×10(6)/L), positive visual xanthochromia in 4 out of 5 ASAH, and positive spectrophotometric xanthochromia in 5 out of 5 ASAH. All ASAH patients were neurologically intact after intervention. No deaths or missed ASAH were reported. Angiographies were performed on 127 patients (19.5%) of which 47 (34.1%) had positive xanthochromia (visual or spectrophotometric). CONCLUSIONS: Considering the low prevalence of ASAH following an NHCT, intense resources were utilized to identify all 5 ASAH. Lumbar puncture analyses combining red blood cell count, visual and spectrophotometric xanthochromia identified all ASAH, allowing intervention and a positive clinical outcome. Our data support 1) that LP identifies the presence of a ruptured ASAH after an NHCT and 2)` that a guide to define a subpopulation of patients who would benefit from a lumbar puncture after an NHCT would be desirable.

Predictive value of S-100ß protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis.

OBJECTIVES: To determine the ability and accuracy of the S-100ß 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-100ß 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-100ß within 24 hours after traumatic brain injury. There was a significant positive association between S-100ß protein concentrations and mortality (12 studies: geometric mean ratio 2.55, 95% confidence interval 2.02 to 3.21, I(2)=56%) and score ≤ 3 (18 studies: 2.62, 2.01 to 3.42, I(2)=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-100ß 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-100ß protein concentrations are significantly associated with unfavourable prognosis in the short, mid, or long term. Optimal thresholds for discrimination remain unclear. Measuring the S-100ß 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.

Stability of norepinephrine infusions prepared in dextrose and normal saline solutions.

PURPOSE: Norepinephrine (NE) infusions are commonly used in the intensive care unit and in the operating room. Data on long term stability of NE solutions are lacking. This prospective study was designed to evaluate the stability of NE, in dextrose (5%) in water (D5W) and in normal saline (NS) solutions, for a period up to seven days. METHODS: We prepared norepinephrine solutions in quadruplicate, by aseptically diluting 1 mg NE in 250 mL of D5W or NS and 4 mg NE in 250 mL of D5W or NS (final concentrations, 4 microg x mL(-1) and 16 micro x mL(-1), respectively) and stored the solutions at room temperature under ambient light. We sampled the solutions, in duplicate, at times 0, 24, 48, 72, 120, and 168 hr and stored them at -80 degrees C for later assay. Norepinephrine concentrations were measured by high-performance liquid chromatography with electrochemical detection (coefficient of variation 4.6%). Statistical analysis was done by nonparametric, repeated measures ANOVA (Friedman test). RESULTS: There was no significant decrease in NE concentration for either, NE 4 microg x mL(-1) in D5W or NS (P = 0.09 and 0.11, respectively) or for NE 16 microg x mL(-1) in D5W or NS (P = 0.18 and 0.40, respectively). The ratios of NE concentration at 168 hr, compared to baseline, were 95.7% and 96.4%, for NE 4 microg x mL(-1) in D5W and NS, respectively, and 104.5% and 96.4%, for NE 16 microg x mL(-1) in D5W and NS, respectively. CONCLUSION: Norepinephrine solutions, in concentrations commonly used in the clinical setting, are chemically stable for seven days, at room temperature and under ambient light, when diluted either in D5W or NS.