Serum NGAL is a potential biomarker for the clinical outcomes of PCAS patients. As described below, serum NGAL predicted mortality in OHCA, and had potential predictive value for the neurological outcomes in some studies. However, because the studies did not compare its predictive value with that of other biomarkers, it was not possible to conclude that serum NGAL can predict the neurological outcomes of OHCA patients. Elmer et al. reported that serum NGAL was a stronger predictor of hospital mortality in cardiac arrest patients than other markers, such as NSE, S100B protein, and high-mobility group protein 1 [9]. Park et al. reported that serum NGAL predicted AKI in OHCA patients admitted to an intensive care unit, as well as the 30-day survival and neurological outcomes in these patients [8]. In the present study, serum NGAL on day 2 showed potential predictive value for the neurological outcomes at discharge of OHCA patients. However, serum NGAL on day 1 was not predictive of these outcomes, a result that differs from those reported by Park et al., who measured NGAL upon admission to the intensive care unit. In our study, 65% (28/43) of patients received therapeutic hypothermia, which might affect the NGAL concentration, as has been reported for other biomarkers [11, 12].
NSE is one of the most frequently measured biomarkers in PCAS patients. A recent prospective study recommended a cutoff value of 33 ng/mL for NSE measured between 24 and 72 h after ROSC in patients who did not undergo therapeutic hypothermia [13]. Additionally, a post hoc analysis of a recent randomized controlled study of therapeutic hypothermia showed that there was no NSE difference between the target temperature groups, but the cutoff value was >33 ng/mL [3]. In this study, we measured serum NSE on day 2, which was the recommended time in a previous study [3]. In our study, the cutoff value for NSE on day 2 (about 24–72 h) was 28.8 ng/mL, and the false-positive rate was 0%, below, which was lower than that in a previous study [3], possibly because most of the patients with CPC1–2 showed good recovery (CPC1) and the NSE concentration was not increased in the favourable outcome group.
In the present study, serum NGAL showed potential value for predicting the prognosis of PCAS patients, and it was significantly different between the favourable and unfavourable outcomes groups on day 2. However, based on the ROC curve analysis, serum NGAL on day 2 did not show sufficient sensitivity and specificity. At a cutoff value of 304 ng/mL, the false-positive rate was 24%. Moreover, the area under the ROC curve for NGAL (0.830) was equivalent to that of NSE (0.918). Therefore, our data did not show superiority of serum NGAL over serum NSE as a biomarker for predicting the neurological outcomes of PCAS patients.
Serum NGAL is well known as a biomarker for AKI, and it is possible that AKI might affect serum NGAL concentrations [4, 5]. Therefore, the predictive value of serum NGAL in PCAS patients with AKI is unclear. Our study included five patients whose estimated glomerular filtration rate was <20 mL/min/1.73 m2. Therefore, these five patients were eliminated from our data, the area under the ROC curve was 0.978 for serum NGAL, which was superior to that of NSE (0.923). At the cutoff value of 304 ng/mL for serum NGAL, the sensitivity and specificity were 88% and 100%, respectively, which were equivalent to those of NSE at a cutoff value of 28.8 ng/dL. Based on these data, if the effect of AKI can be eliminated, serum NGAL could be a useful predictive biomarker for PCAS patients.
Finally, further study is needed to solve these questions and investigate the potential of serum NGAL for predicting the prognosis of PCAS patients.
Our study has some limitations to mention. First, this study was performed at a single centre and involved a small number of patients, which may limit the strength of the conclusions. Second, the neurological outcomes were assessed at hospital discharge, and some patients experience neurological improvement after discharge. Third, the blood samples could be collected at any time of day, and could range by up to 24 h among patients.