Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial
Lauri Wihersaari, Nicholas J. Ashton, Matti Reinikainen, Pekka Jakkula, Ville Pettilä, Johanna Hästbacka, Marjaana Tiainen, Pekka Loisa, Hans Friberg, Tobias Cronberg, Kaj Blennow, Henrik Zetterberg, Markus B. Skrifvars, the COMACARE STUDY GROUP, Raili Laru‐Sompa, Anni Pulkkinen, Mikko Reilama, Sinikka Tolmunen, Minna Bäcklund, Jonna Heinonen, Johanna Hästbacka, Pekka Jakkula, Nina Lundbom, Marcus Norrgård, Marjatta Okkonen, Ville Pettilä, Markus B. Skrifvars, Tarja Suhonen, Marjaana Tiainen, Tuukka Tikka, Marjut Timonen, Jussi Toppila, Miia Valkonen, Erika Wilkman, Teemu Hult, Tuomas Oksanen, Stepani Bendel, Elina Halonen, Sari Rahikainen, Saija Rissanen, Eija Vaskelainen, Tanja Eiserbeck, Sirkku Heino, Helena Jyrkönen, Matti Reinikainen, Johanna Räsänen, Tero Surakka, Talvikki Koskue, Petteri Kujala, Pekka Loisa, Marika Lähde, Jari Kalliomäki, Sari Karlsson, Atte Kukkurainen, Simo Varila
Abstract
Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO2), arterial oxygen tension (PaO2), and mean arterial pressure (MAP). We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1–2 and poor outcome as CPC 3–5. Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11–31) pg/ml in patients with good outcome and 2343 (587–5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97–1.00) at 24 h, 0.98 (0.97–1.00) at 48 h, and 0.98 (0.95–1.00) at 72 h. NfL concentrations were lower in the higher MAP (80–100 mmHg) group than in the lower MAP (65–75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO2 and PaO2 targets did not associate with NfL levels. NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.