{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:01:46Z","timestamp":1789794106255,"version":"4.0.1"},"reference-count":15,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Bystander cardiopulmonary resuscitation (CPR) improves outcome after out-of-hospital cardiac arrest (OHCA), but whether its neurological benefit operates solely through prehospital return of spontaneous circulation (ROSC) is unresolved. We quantified the mediated and unmediated components. Methods: Retrospective cohort study of the Korean nationwide OHCA registry (2009\u20132024) in adults with cardiac or respiratory arrest, excluding arrests witnessed by on-duty personnel. The primary outcome was favorable neurological survival (Cerebral Performance Category 1\u20132 at discharge) defined across the whole cohort; prehospital ROSC was the mediator. Effects were decomposed with logistic models, including an exposure-by-mediator interaction. Results: Among 80,784 patients, 59,982 (74.2%) received bystander CPR. The natural direct effect was +1.24 percentage points (95% CI 0.97 to 1.51). With prehospital ROSC fixed by intervention at not achieved\u2014for everyone, not only for patients observed to lack it\u2014the controlled direct effect was +0.65 (0.41 to 0.85) and +0.70 (0.46 to 0.94; E-value 2.43, lower confidence limit 1.92) on restriction to 2016\u20132024. The total effect was +5.24 points (4.85 to 5.60), 76.4% of it ROSC-mediated. No survival effect was demonstrable at that value (+0.25, \u22120.14 to 0.61), and adjustment for initial rhythm left the neurological estimate indistinguishable from zero (+0.36, \u22120.02 to 0.69). Conclusions: A small component of the neurological benefit may lie outside the prehospital ROSC pathway\u2014not outside restored circulation altogether since such survivors regained circulation in hospital\u2014though most was ROSC-mediated. It is not established: an unmeasured confounder of moderate strength, or initial rhythm acting as a confounder rather than a mediator, would account for it. The estimates apply to events with ascertained bystander-CPR status, undocumented in 70% of otherwise eligible events. Prehospital ROSC may nonetheless understate the value of bystander response.<\/jats:p>","DOI":"10.3390\/jcm15187095","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"7095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Do Chest Compressions Benefit the Brain Beyond Restoring Circulation? ROSC-Mediated and ROSC-Independent Pathways of Bystander CPR After Out-of-Hospital Cardiac Arrest"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9228-3674","authenticated-orcid":false,"given":"Gyuchong","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-0090","authenticated-orcid":false,"given":"Youdong","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"ref_1","first-page":"110704","article-title":"European registry of cardiac arrest study THREE (EuReCa-THREE)\u2014EMS response time influence on outcome in Europe","volume":"223","author":"Wnent","year":"2025","journal-title":"Resuscitation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1161\/CIR.0000000000001412","article-title":"2026 heart disease and stroke statistics: A report of US and global data from the American Heart Association","volume":"153","author":"Palaniappan","year":"2026","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S366","DOI":"10.1161\/CIR.0000000000000916","article-title":"Part 3: Adult basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care","volume":"142","author":"Panchal","year":"2020","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.resuscitation.2021.02.009","article-title":"European Resuscitation Council guidelines 2021: Basic life support","volume":"161","author":"Olasveengen","year":"2021","journal-title":"Resuscitation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1161\/01.CIR.83.5.1832","article-title":"Improving survival from sudden cardiac arrest: The \u201cchain of survival\u201d concept","volume":"83","author":"Cummins","year":"1991","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1001\/jama.1990.03440080084029","article-title":"Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation","volume":"263","author":"Paradis","year":"1990","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.resuscitation.2014.10.017","article-title":"Return of consciousness during ongoing cardiopulmonary resuscitation: A systematic review","volume":"86","author":"Olaussen","year":"2015","journal-title":"Resuscitation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e020825","DOI":"10.1161\/JAHA.121.020825","article-title":"Insights from the ventricular fibrillation waveform into the mechanism of survival benefit from bystander cardiopulmonary resuscitation","volume":"10","author":"Bessen","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, Y., Yue, P., Wu, Y., Li, J., Lei, Y., Gao, D., Liu, J., and Han, P. (2021). Trend in survival after out-of-hospital cardiac arrest and its relationship with bystander cardiopulmonary resuscitation: A six-year prospective observational study in Beijing. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-02446-z"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kong, S.Y., and Jeong, S. (2026). A moderated mediation analysis of timely EMS activation and bystander CPR in the association between regional deprivation and outcomes following out-of-hospital cardiac arrest. 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