BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Alma Mater Studiorum University of Bologna Bologna Italy

Cardiothoracic Surgery Department Maastricht University Medical Center and Cardiovascular Research Institute Maastricht Maastricht University Maastricht Netherlands

Centre Hospitalier Regional Universitaire Lille Hôpital Roger Salengro Lille France

Centro de Investigacion en Red de Enfermedades Respiratorias Instituto de Salud Carlos 3 Barcelona Spain

Critical Care Department Alvaro Cunqueiro University Hospital Vigo Spain

Critical Care Department Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Allergy Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN USA

Department of Anesthesia and Intensive Care Istituto Mediterraneo per i trapianti e Terapie ad alta specializzazione Palermo Italy

Department of Anesthesia Intensive Care and Emergency Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Milan Italy

Department of Anesthesiology and Intensive Care 1st Medical Faculty General University Hospital Prague Czech Republic

Department of Critical Care University of Pittsburgh Medical Center University of Pittsburgh Pittsburgh PA USA

Department of Intensive Care Medicine St Vincent's Hospital Sydney NSW Australia

Department of Medicine 1 Intensive Care Unit 13i2 Center of Excellence in Medical Intensive Care Medical University of Vienna Vienna Austria

Department of Medicine and Center for Acute Respiratory Failure Irving Medical Center Columbia University New York NY USA

Department of Pathophysiology and Transplantation University of Milan Italy

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Department of Surgical Sciences University of Turin Turin Italy

Dipartimento di Scienze Biotecnologiche di Base Cliniche Intensivologiche e Perioperatorie Università Cattolica del Sacro Cuore Rome Italy

Dipartimento di Scienze dell'Emergenza Anestesiologiche e della Rianimazione Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

ECMO Center Ljubljana Slovenia

ECMO Centre Karolinska Karolinska University Hospital Stockholm Sweden

Hamad Medical Corporation Doha Qatar

INSERM 1166 Institute of Cardiometabolism and Nutrition Sorbonne Université Paris France

Kuwait Extracorporeal Life Support Program Jaber Al Ahmad Alsabah Hospital Kuwait City Kuwait

Meijer Heart Center Butterworth Hospital Spectrum Health Grand Rapids MI USA

Ospedale San Gerardo Università degli Studi Di Milano Bicocca Monza Italy

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

School of Medicine University of Maryland Baltimore MD USA

Service de Médecine Intensive Réanimation Institut de Cardiologie Assistance Publique Hôpitaux de Paris Hôpital Pitié Salpêtrière Paris France

Shock Organ Dysfunction and Resuscitation Vall d'Hebron Institut de Recerca Barcelona Spain

Statistics and Data Management Services Istituto Mediterraneo per i trapianti e Terapie ad alta specializzazione Palermo Italy

The University of Oklahoma Health Sciences Center University of Oklahoma Oklahoma City OK USA

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