New research published in the Journal of the American Medical Association (JAMA) reveals a correlation between the brain injury biomarker, neurofilament light (Nf-L), and outcomes of cardiac arrest patients.
These patients often suffer from hypoxic Ischemic Brain Injury (HIBI), a condition that results from poor blood flow to the brain during the arrest, and is the leading cause of death and morbidity in patients who suffer a cardiac arrest. Nf-L is released into the blood stream within 48 hours of white matter damage and axonal injury to the brain. The study’s findings suggest that monitoring the level of Nf-L in post-cardiac arrest patients can help to predict their possibility of neurological recovery.
“Our study is the largest and most comprehensive review on this topic to date and has the potential to change current guidelines on the use of brain biomarkers in predicting neurologic outcome for post-cardiac arrest patients,” said co-first author Dr. Kiran Rikhraj, a third-year resident at the UBC Department of Emergency Medicine and Vancouver General Hospital.
Our study is the largest and most comprehensive review on this topic to date and has the potential to change current guidelines on the use of brain biomarkers in predicting neurologic outcome for post-cardiac arrest patients.
— Dr. Kiran Rikhraj
Current guidelines in predicting HIBI outcomes recommend the use of multiple modalities such as clinical exam, EEG, SSEP and neuroimaging techniques—all of which often require expert interpretation and significant resources. On the other hand, brain biomarkers released into the blood are an easily measurable and widely interpretable tool.
Previous research on biomarkers in cardiac arrest patients have primarily focused on neuron-specific enolase (NSE) and S100 calcium-binding protein β (S100β). In this study, the researchers examined the prognostic utility of NSE and S100β as well as four other brain injury biomarkers—glial fibrillary acidic protein (GFAP), neurofilament light (Nf-L), tau, and ubiquitin carboxyl hydrolase L1 (UCH-L1)—and demonstrated that Nf-L had the highest accuracy in predicting unfavourable neurological outcome in post-cardiac arrest patients compared to the other biomarkers.
Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, the researchers identified 86 studies with 10,567 patients that were included in the review. They then extracted data on biomarker accuracy at 24, 48, and 72 hours after arrest. Using a two-stage random-effects statistical model, they calculated a summary receiver operating characteristic (SROC) curve for each biomarker at 48 hours following cardiac arrest and also estimated optimal thresholds for each biomarker for particular weights of specificity.
Our analysis indicated that biomarkers that reflect axonal injury, such as Nf-L and Tau, had the highest accuracy in predicting an unfavourable neurologic outcome in post-cardiac arrest patients.
— Dr. Kiran Rikhraj
“Our analysis indicated that biomarkers that reflect axonal injury, such as Nf-L and Tau, had the highest accuracy in predicting an unfavourable neurologic outcome in post-cardiac arrest patients. Current guidelines only include measurement of NSE as a prognostication tools and our research suggests that Nf-L and Tau should be included as well. However, we need further prospective studies with standardized biomarker collection, timing, and analytical platforms to really show the promise of using these novel biomarkers in predicting outcomes for these patients.” said Dr. Rikhraj
The study was supported by the University of British Columbia Division of Critical Care, Djavad Mowafaghian Centre for Brain Health, and ICORD.
