Predictive performance of plasma neutrophil gelatinase-associated lipocalin for neurologic outcomes in out-of-hospital cardiac arrest patients treated with targeted temperature management: A prospective observational study

Abstract

Few studies have demonstrated the prognostic potential of neutrophil gelatinase-associated lipocalin (NGAL) in post-cardiac arrest patients. This study evaluated the usefulness of plasma NGAL in predicting neurologic outcome and mortality in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). A prospective observational study was conducted between October 2013 and April 2016 at a single tertiary hospital. We enrolled 75 patients treated with TTM and collected their demographic data, cardiopulmonary resuscitation-related information, data on plasma NGAL concentration, and prognostic test results. Plasma NGAL was measured at 4 hours after return of spontaneous circulation (ROSC). The primary endpoint was the neurologic outcome at discharge and the secondary outcome was 28-day mortality. Neurologic outcomes were analyzed using a stepwise multivariate logistic regression while 28-day mortality was analyzed using a stepwise Cox regression. The predictive performance of plasma NGAL for neurologic outcome was measured by the area under the receiver operating characteristic curve and the predictability of 28-day mortality was measured using Harrell C-index. We also compared the predictive performance of plasma NGAL to that of other traditional prognostic modalities for outcome variables. Thirty patients (40%) had good neurologic outcomes and 53 (70.7%) survived for more than 28 days. Plasma NGAL in patients with good neurologic outcomes was 122.7 ± 146.7 ng/ml, which was significantly lower than that in the poor neurologic outcome group (307.5 ± 269.6 ng/ml; P < .001). The probability of a poor neurologic outcome was more than 3.3-fold in the NGAL >124.3 ng/ml group (odds ratio, 3.321; 95% confidence interval [CI], 1.265-8.721]). Plasma NGAL in the survived group was significantly lower than that in the non-survived group (172.7 ± 191.6 vs 379.9 ± 297.8 ng/ml; P = .005). Plasma NGAL was significantly correlated with 28-day mortality (hazard ratio 1.003, 95% CI 1.001-1.004; P < .001). The predictive performance of plasma NGAL was not inferior to that of other prognostic modalities except electroencephalography. Plasma NGAL is valuable for predicting the neurologic outcome and 28-day mortality of patients with OHCA at an early stage after ROSC.This study was registered at ClinicalTrials.gov on November 19, 2013 (Identifier: NCT01987466).

Figure 1

Flow diagram of the study participants. ROSC, return of spontaneous circulation; TTM, targeted temperature management; ESRD, end-stage renal disease; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 2

Predictive power of each prognostic test for neurologic outcomes and 28-day mortality. (A) Receiver operating characteristics curve for each prognostic factor to predict poor neurologic outcome. (B) Harrell C-index comparison for each prognostic factor to predict 28-day mortality: AUC, area under the curve; CI, confidence interval; NGAL, neutrophil gelatinase-associated lipocalin; NSE, neuron specific enolase; EEG, electroencephalogram; SSEP, somatosensory evoked potential; MRI, magnetic resonance imaging.

Figure 3

Kaplan–Meier survival curves for 28-day mortality based on the cut-off value of neutrophil gelatinase associated lipocalin (NGAL). ROSC, return of spontaneous circulation.