Maayke Hunfeld

35 Review neuromonitoring the follow-up interval (5 yr after event), the outcome assessment (HUI:1 and GOS) was done by telephone interview making bias by caregivers possible. Biomarkers One pilot randomized controlled trial, two observational prospective studies and one retrospective study are published in children after CA (Supplemental Table 8, Supplemental Digital Content 2, http://links.lww.com/PCC/B352 ). Kramer et al ((39), n=95), Fink et al ((40), n=43) and Topjian et al ((41), n=35) found a significant correlation between high levels of neuron specific enolase (NSE) post ROSC and death 24 hours post ROSC. Topjian et al found no significant differences in S-100b levels in patients with good versus poor outcome, however in the study by Fink et al S-100B levels were increased in the poor outcome group from 48 hours after ROSC (p<0.05). For S-100B, in both the study by Topjian et al and in the study by Fink et al, increased levels from 48 hours and 24 hours respectively post ROSC were significantly associated with nonsurvival (40, 41). Fink et al concluded that S-100B and NSE are superior in predicting outcome at 6 months compared to clinical predictors (duration CPR, first lactate, first blood pH) (40). Recently Fink et al (2018) described biomarker trajectories in patient groups with different duration of targeted temperature management, but no association with outcome was shown (42). The most important limitations of these studies are as follows: Only one study was a pilot randomized controlled trial (42). However, the purpose of this randomized controlled trial was not neuroprognostication but rather to test the hypothesis that 72 versus 24 hours of hypothermia would produce more favorable serum biomarkers after pediatric CA. All studies were single center with mostly a small cohort (median n=39, IQR 34-82). Kramer et al also included neonates (39). As already described in other neuromonitoring modalities, outcome scales were gross (no neuropsychological assessments) and short term, ranging from hospital discharge up to 6 months post CA. When outcome was nonsurvival, the cause was not specified. Discussion This systematic review describes several methods of neuromonitoring in children after CA with the purpose of early neuroprognostication. It is noteworthy that even with generous inclusion criteria, the total number of patients in the (included) studies is only 1564, which is a fraction of the total number of CAs over a 20-year period. This 2