BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

2 Department of Anesthesiology Centre of Anesthesia Intensive Care and Pain Management Vilnius University Hospital Santariskiu Klinikos Vilnius Lithuania

2nd Department of Internal Medicine Cardiovascular Medicine General Teaching Hospital and 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Adult Intensive Care Services The Prince Charles Hospital Brisbane Australia

Cardiac Intensive Care Unit Johns Hopkins Hospital Baltimore MD USA

Cardiac Surgery Unit Cardiac Thoracic and Vascular Department Niguarda Hospital Milan Italy

Cardiac Surgery Unit Fondazione IRCCS San Gerardo dei Tintori Monza Italy

Cardiac Surgery Unit IRCCS Humanitas Research Hospital Rozzano MI Italy

Cardio Thoracic Surgery Department Cardiovascular Research Institute Maastricht Maastricht University Medical Centre P Debyelaan 25 6202AZ Maastricht The Netherlands

Cardiothoracic Intensive Care Unit National University Heart Centre National University Hospital Singapore Singapore

Center for Cardiac Intensive Care Beijing Institute of Heart Lung and Blood Vessels Diseases Beijing Anzhen Hospital Capital Medical University Beijing China

Departamento de Anestesia ECMO Unit Clínica Las Condes Las Condes Santiago Chile

Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation IRCCS ISMETT Palermo Italy

Department of Cardiac Surgery Department of Cardiovascular Sciences University of Leuven Louvain Belgium

Department of Cardiac Surgery Hôpitaux Universitaires Henri Mondor Assistance Publique Hôpitaux de Paris Creteil France

Department of Cardiac Surgery Karl Landsteiner University University Clinic St Pölten St Pölten Austria

Department of Cardiac Surgery Leipzig Heart Center Leipzig Germany

Department of Cardiac Surgery Louis Pradel Cardiologic Hospital Lyon France

Department of Cardiac Surgery Medical Faculty Heinrich Heine University Duesseldorf Germany

Department of Cardiac Surgery Medical University of Vienna Vienna Austria

Department of Cardiology Fundación Cardiovascular de Colombia Bucaramanga Colombia

Department of Cardiothoracic Surgery University Medical Center Regensburg Regensburg Germany

Department of Cardiovascular Surgery Ziekenhuis Oost Limburg Genk Belgium

Department of Intensive Care Adults and Cardiology Erasmus MC Rotterdam The Netherlands

Department of Intensive Care Medicine and Cardiovascular Research Institute Maastricht Maastricht The Netherlands

Department of Intensive Care Medicine Center of Applied Medical Research St Vincent's Hospital Darlinghurs NSW Australia

Department of Medicine and Surgery Cardiac Surgery Unit University of Parma University Hospital of Parma Parma Italy

Department of Thoracic and Cardiovascular Surgery Korea University Anam Hospital Seoul South Korea

Departments of Medicine and Surgery University of Maryland Baltimore USA

Division of Cardiac Surgery Cardiothoracic Department University Hospital of Udine Udine Italy

Division of Cardiac Surgery IRCCS Azienda Ospedaliero Universitaria Di Bologna Bologna Italy

Division of Cardiac Surgery Memorial Healthcare System Hollywood FL 33021 USA

Division of Cardiothoracic and Vascular Surgery Pontchaillou University Hospital Rennes France

Division of Cardiovascular and Thoracic Surgery Department of Surgery Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand

Intensive Care Unit Spedali Civili University Hospital Brescia Italy

Intensive Care Unit The Alfred Hospital Melbourne VIC Australia

IU Health Advanced Heart and Lung Care Indiana University Methodist Hospital Indianapolis IN USA

Ospedale del Cuore Fondazione Toscana G Monasterio Massa Italy

SOD Cardiochirurgia Ospedali Riuniti 'Umberto 1 Lancisi Salesi' Università Politecnica delle Marche Ancona Italy

University of New South Wales Sydney Australia

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