Early Blood Biomarkers and MRI Injury After Cardiac Arrest: Secondary Analysis of the 2017-2020 "Personalized Outcomes After Child Cardiac Arrest" Study

Anna M Janas; Kristen R Miller; Rafael Ceschin; Peter M Mourani; Christopher M Ruzas; Tellen D Bennett; Ericka L Fink; Aline B Maddux; Personalizing Outcomes After Child Cardiac Arrest (POCCA) Investigators

doi:10.1097/PCC.0000000000003756

Early Blood Biomarkers and MRI Injury After Cardiac Arrest: Secondary Analysis of the 2017-2020 "Personalized Outcomes After Child Cardiac Arrest" Study

Pediatr Crit Care Med. 2025 Apr 28. doi: 10.1097/PCC.0000000000003756. Online ahead of print.

Collaborators

Personalizing Outcomes After Child Cardiac Arrest (POCCA) Investigators:
Patrick M Kochanek⁸, Robert R S B Clark⁸, Anthony Fabio⁹, Chunya Wang⁹, David Maloney¹⁰, Sue R Beers⁹, Tamara L Haller⁹, Amery Treble-Barna⁹, Jose Pineda¹¹, Christopher Newth¹², Alexis A Topjian¹³, Craig A Press¹³, Frederick Willyerd¹⁴, Elizabeth A Hunt¹⁵, Ashley Siems¹⁵, Melissa G Chung¹⁶, Smith Lincoln¹⁷, J Wesley Diddle¹⁸, Jason Patregnani¹⁸, Juan Piantino¹⁹, Binod Balakrishnan²⁰, Michael T Meyer²⁰, Stuart Friess²¹, Ashok Panigrahy⁹, Subramanian Subramanian⁹, Srikala Narayanan⁹, Stefan Bluml¹², Jessica Wisnowski¹², Julia Wallace⁸, Rachel Berger⁹, Hulya Bayir⁹, Leslie Doughty²², Karen Hallermeier Walson²³, Pamela Rubin⁹, Vince Lee⁹

Affiliations

¹ Department of Pediatrics, Section of Critical Care, University of Colorado School of Medicine and Children's Hospital of Colorado, Aurora, CO.
² Department of Pediatric Radiology, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh, PA.
³ Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA.
⁴ Department of Pediatrics, Section of Critical Care, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR.
⁵ Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO.
⁶ Department of Critical Care Medicine, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh, PA.
⁷ Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA.
⁸ UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
⁹ University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ PMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
¹¹ Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Children's Hospital of Los Angeles, Los Angeles, CA, USA.
¹³ Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁴ Phoenix Children's Hospital, Phoenix, AZ, USA.
¹⁵ Johns Hopkins Children's Center, Baltimore, MD, UA.
¹⁶ Nationwide Children's Hospital, Columbus, OH, USA.
¹⁷ University of Washington School of Medicine, Seattle, WA, USA.
¹⁸ Children's National Medical Center, Washington, DC, USA.
¹⁹ Oregon Health & Science University, Portland, OR, USA.
²⁰ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²¹ St Louis Children's Hospital, St Louis, MO, USA.
²² Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²³ Children's Healthcare of Atlanta, Atlanta, GA, USA.

PMID: 40293338
DOI: 10.1097/PCC.0000000000003756

Abstract

Objectives: Brain MRI is used to inform prognosis of pediatric cardiac arrest (CA). We analyzed the association between early levels of four brain injury biomarkers and pattern of brain injury on MRI.

Design, setting, and patients: This secondary analysis of a multicenter prospective cohort study in 14 U.S. hospitals (from May 16, 2017, to August 19, 2020) recruited children 48 hours to 17 years old who were resuscitated after CA and had a brain MRI within 14 days postarrest.

Interventions: None.

Measurements and main results: Brain MRI injury score was calculated as a sum of T2- and diffusion-weighted imaging lesions. We used the Kruskal-Wallis test to compare maximum biomarker values on days 1-3 between three categories of MRI injury severity (i.e., no injury, mild-moderate injury, and severe injury). Maximum neurofilament light chain (NfL), tubulin-associated unit, glial fibrillary acidic protein, and ubiquitin C-terminal hydrolase L1 levels were associated with severity of total injury, gray matter injury, and white matter injury. Using logistic regression, individual biomarker levels were associated with presence of injury on MRI after adjusting for age, presence of congenital heart disease, and severity of illness using Pediatric Index of Mortality 3 score. Of 40 patients with injury on MRI and 1-year outcome data, median (interquartile range [IQR]) NfL levels were higher in the 15 patients who died compared with the 21 patients with favorable outcome (7.10 pg/mL [IQR, 5.94-7.51 pg/mL] vs. 5.10 pg/mL [IQR, 4.10-5.94 pg/mL]; log transformed; p < 0.001), but we failed to identify a difference in levels between those with unfavorable outcome (Vineland Adaptive Behavior Score < 70, n = 4) vs. favorable outcome.

Conclusions: Blood biomarkers measured early after injury are associated with MRI injury and may provide additional information for prognostication when incorporated in a multimodal evaluation.

Keywords: biomarker; cardiac arrest; magnetic resonance imaging; neuroimaging; pediatrics.

Early Blood Biomarkers and MRI Injury After Cardiac Arrest: Secondary Analysis of the 2017-2020 "Personalized Outcomes After Child Cardiac Arrest" Study

Authors

Collaborators

Affiliations

Abstract

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