Every second counts: Association between activated clotting time and neurologic injury in neonatal ECMO

Background: Extracorporeal membrane oxygenation (ECMO) is a critical support modality for patients with reversible cardiopulmonary failure. Despite its benefits, ECMO is associated with neurologic adverse events (NAE), including seizures and intracranial hemorrhage. Data on modifiable risk factors for NAE in neonates remain limited. This study aimed to assess the incidence, nature, and predictors of NAE in a neonatal ECMO cohort, with a particular focus on anticoagulation state. Methods: This retrospective single-center study included 53 neonates (<30 days old) who were supported by ECMO between 2009 and 2025. Patients with major congenital heart disease were excluded. Clinical data, including neurologic outcomes, cranial ultrasound findings, seizure history, and detailed anticoagulation metrics (activated clotting time [ACT]), were analyzed. Patients were grouped based on the occurrence of NAEs. Results: NAEs occurred in 32% of patients and included seizures (13%), abnormal cranial ultrasound findings (21%). 4 (7.5%) patients suffered long-term neurologic sequelae. Patients with NAEs had significantly higher mean ACT levels and higher mean ACT standard deviation, and longer durations of ACT values above the therapeutic range. On multivariable analysis, higher mean ACT, and surfactant administration were independently associated with NAEs. Surfactant use likely reflected underlying pulmonary disease severity. Mortality was higher among patients with NAEs but did not reach statistical significance. Conclusion: This study demonstrates that both higher ACT levels and greater ACT variability are associated with increased NAE in neonates undergoing ECMO. These findings underscore the need for vigilant anticoagulation management, with attention not only to keeping ACT within the target range but also to maintaining its stability, to optimize neurologic outcomes.