The accuracy of various neuro-prognostication algorithms and the added value of neurofilament light chain dosage for patients resuscitated from shockable cardiac arrest: An ancillary analysis of the ISOCRATE study

Purpose: In current guidelines, neurological prognostication after cardiopulmonary resuscitation is based on a multimodal approach bundled in algorithms. Biomarkers are of particular interest because they are unaffected by interpretation bias. We assessed the predictive value of serum neurofilament light chains (NF-L) in patients with a shockable rhythm who received cardiopulmonary resuscitation, and evaluated the predictive value of a modified algorithm where NF-L dosage is included.

Methods: All patients who were included participated in the randomized ISOCRATE trial. NF-L values 48 h after ROSC were compared for patients with a good (Cerebral Performance Category (CPC) 1 or 2) and a poor prognosis (CPC 3 to 5 or death). The benefit of adding NF-L dosage to the current guideline algorithm was then assessed for NF-L thresholds of 500 and 1,200 pg/ml as previously described.

Results: NF-L was assayed for 49 patients. In patients with good versus those with poor outcomes, median NF-L values at 48 h were 72 ± 78 and 7,755 ± 9,501 pg/ml respectively (P < 0.0001; AUC [95 %CI] = 0.87 [0.74;0.99]). The sensitivity of the modified ESICM/ERC 2021 algorithm after adding NF-L with thresholds of 500 and 1,200 pg/ml was 0.74 (CI 95% 0.51-0.88) and 0.68 (CI 95% 0.46-0.86), respectively, versus 0.53 (CI 95% 0.32-0.73) for the unmodified algorithm. In three instances the specificity was 1.

Conclusion: High NF-L plasma levels 48 h after cardiac arrest was significantly associated with a poor outcome. Adjunction to the current guideline algorithm of an NF-L assay with a 500 pg/ml threshold 48 h after cardiac arrest provided the best sensitivity compared to the algorithm alone, while specificity remained excellent.