Plasma biomarkers as prognostication in patients receiving extracorporeal membrane oxygenation

Introduction: Neurological complications in VA-ECMO beget a 7-15% mortality rate; however, existing literature demonstrates that neuromonitoring reduces the rate of complications. There is an increasing need for easily measured, accurate markers that can predict neurological injury. We propose that plasma biomarkers such as Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), and Tau can be utilized for prognostication of neurologic outcomes on ECMO. We hypothesised that patients with higher levels of inflammatory biomarkers will be at higher risk for neurologic complications. Methods: In this pilot prospective, cohort study, patients were consented within 24 hours of cannulation and followed over duration of VA-ECMO course. Peak concentrations of plasma biomarkers were used for analysis. Samples were taken daily for first 7 days and every other day afterwards as long as patient remained in the ICU. Outcomes were determined by the modified Rankin Scale (mRS) with a favorable outcome of mRS < 4. Statistical analyses used STATA v17 to calculate the Area Under ROC curves to determine sensitivity and specificity. Results: 20 patients were enrolled. Median age was 48.5 (41.5-62 IQR) yrs, and patients were 55% female. The median peak concentration values of GFAP, NFL, and Tau were 382.3 pg/ml (100.8-5,516.4), 8,306.7 pg/ml (2,338.9-13,577.2), and 1,278.4 pg/ml (318.7-3,447.4), respectively. There were 15 patients (75%) with unfavourable neurologic outcome at discharge, 17 patients had acute brain injury (85%), 10 patients had thromboembolic events (50%), and 14 patients had hemorrhagic events (70%). In prognostication of acute brain injury in patients, the plasma biomarkers GFAP, NFL and Tau achieved an AUC of 0.84, 0.73, and 0.73 respectively. Furthermore, GFAP, NFL and Tau achieved an AUC of 0.70, 0.81, and 0.70 for prediction of hemorrhagic events on ECMO. Conclusions: We identify three key plasma biomarkers, GFAP, NFL and Tau, that have the groundbreaking potential to assist prognostication of acute brain injury and hemorrhagic events on ECMO. We strongly recommend further research to identify feasibility and utility of novel biomarkers in the context of VA-ECMO and neurological complications to understand which combination of plasma biomarkers has the highest clinical yield.