Quantitative pupillometry and neuron-specific enolase independently predict return of spontaneous circulation following cardiogenic out-of-hospital cardiac arrest: a prospective pilot study

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0–2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07–0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93–0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.