Therefore, we emphasize that the time-course change in early phase of serum S-100B and NSE levels would offer a more reliable indication of what is happening in the brain of the CA patient, which Fluoro-Sorafenib might be useful for optimization of therapeutic intervention in future cases of CA. However, there are few investigations on the time-course of these biomarkers. Usui and colleagues  reported the detailed time-course of these biomarkers in serum and cerebrospinal fluid every one to two hours within 18 hours after CA in mongrel dog models. Bottiger and colleagues  reported the time-course of human serum S-100B every 15 minutes within 1 hour and at 2, 8, and 24 hours after CA. However, this study by Bottiger and colleagues is limited by the number of subjects.
Therefore, there is no investigation on the time-course of these biomarkers involving a large number of human subjects. The future investigators should put more weight on the time-course change of the biomarkers, especially the changes in early phase (i.e., within 24 hours following CA).The present study identified 24 original articles involving investigation of the clinical usefulness of NSE and S-100B as prognostic predictors of CA patients after CPR. The design adopted varied from study to study, making a systematic literature review extremely difficult [10,40]. The major problems encountered during the review process involved variation or heterogeneity among studies in the following three respects: definitions of outcome to be assessed (e.g.
, some studies adopted grouping criteria for outcome different from others); the value of specificity corresponding to each cut-off value reported for a particular biochemical marker predictive of a poor prognosis (i.e., not always fixed at 100%); and specification of blood sampling time points (i.e., not always uniform application of a blood sampling schedule to all subjects with sampling intervals specified).Consistency in the three respects noted above had not been considered in the five review articles previously published on the same subject [1,2,9,10,40], and the present review is the first attempt to consider it.A recently published article discusses pitfalls in critical care meta-analysis , highlighting publication bias and trial-level heterogeneity as pitfalls to be carefully avoided in a systematic review of observational studies such as the present review.
To avoid publication bias, we performed an extensive literature search to identify all papers published previously on the clinical usefulness GSK-3 of NSE and S-100B in prediction of prognosis after resuscitation from CA and closely reviewed the full-text contents of all papers thus identified. Trial-level heterogeneities encountered in papers reviewed in the present study include grouping criteria for outcome (definitions of outcome), specification of time points for blood sampling, and assay procedures for individual biochemical markers of interest.