g., onset of CA, CPR initiation, or ROSC): Auer and colleagues [24] (n = 17), Tiainen and colleagues Wortmannin ATM [26] (n = 36, 34), Bottiger and colleagues [18] (n = 66), Bassetti and colleagues [33] (n = 60) and Karkela and colleagues [36] (n = 20). However, the sample sizes of these studies were not large. In contrast, four studies including larger numbers of subjects (Grubb and colleagues [14] (n = 143), Reisinger and colleagues [21] (n = 227), Zandbergen and colleagues [22] (n = 407), and Meynaar and colleagues [27] (n = 110)) involved blood sampling as a part of normal intensive care routine with no attention focused on the intervals of sampling points from onset of CA. Many previous studies demonstrated time-dependent changes in blood levels of these biochemical markers after CA [18,21,24,25,28,30,32].

In particular, Bottiger et al. [18] investigated the changes in serum S-100B level within 24 hours after CA in detail, and demonstrated that the serum S-100B level varied every hour.Assessment of the clinical usefulness of S-100B and NSE in predicting post-resuscitative neurological outcome thus requires a study design with particular attention focused on the intervals of sampling points from the onset of CA, although no multicenter prospective study using such a study design has been published to date.DiscussionBiochemical markers in blood samples can be expected to serve as prognostic predictors of CA patient outcome after CPR and be more easily applicable to clinical practice than neuroimaging or electrophysiological findings.

In the present study, we performed a systematic literature review to examine the clinical usefulness of NSE and S-100B (proteins specific to the central nervous system and potential biochemical markers of brain damage) as post-resuscitative predictors of neurological prognosis.Grubb and colleagues [14] performed the multiple logistic regression analysis on mortality in these biomarkers and clinical scores (i.e., arrest rhythm, bystander CPR and GCS score). They showed that NSE was an independently significant predictor among them. Pfeifer and colleagues [25] compared the neurological predictive value between these biomarkers and the clinical predictors, such as time of anoxia, GCS score, presence of bystander CPR, and so on. Prohl and colleagues [39] also compared this value using clinical examination score reflected some brain stem reflexes.

Both studies GSK-3 showed the odds ratio of these clinical predictors was lower than those of NSE and S-100B. Those results indicate that predictive value of biomarkers was superior to that of clinical predictors. Clinical predictors were often affected by the clinical situations (e.g., using of sedative agents, relying on information of emergency medical service personnel who collected information at a chaotic emergency scene).