Observational Study

. 2025 Aug 18;29(1):360.

doi: 10.1186/s13054-025-05606-1.

Liberal or restrictive transfusion for veno-arterial extracorporeal membrane oxygenation patients: a target trial emulation using the OBLEX study data

Le Thi Phuong Thao¹, Hergen Buscher², Tri-Long Nguyen³, Gennaro Martucci⁴, Johannes Gratz^{5

6}, Georg Trummer⁷, Matthieu Schmidt⁸, Melchior Gautier⁸, Alexis Serra⁹, Koji Takeda¹⁰, Jan-Steffen Pooth⁷, Kevin Rahn⁷, Florian Geismann¹¹, Matthias Lubnow¹¹, Andrew Retter¹², Priya Nair², Ruan Vlok¹³, Maithri Siriwardena¹⁴, James Winearls¹⁵, James Walsham¹⁶, David Gattas¹⁷, Anders Aneman¹⁸, Bentley Fulcher¹⁹, Sally Newman², Claire Reynolds²⁰, Anthonio Arcadipane⁴, Kiran Shekar^{14

21}, Carol Hodgson^{19

22}, Vincent Pellegrino²², Thomas Mueller¹¹, Daniel Brodie²³, Zoe McQuilten^{24

25}; International ECMO Network (ECMONet)

Collaborators, Affiliations

Collaborators

International ECMO Network (ECMONet):
Aidan Burrell, Annalie Jones, Emma Martin, Phoebe McCracken, Jayne Sheldrake, Shirley Vallance, Meredith Young, Dee Figures, Maimoonbe Gough, Maree Houbert, James McCullough, Julie Pitman, Mandy Tallott, Danielle Austin, Peter McCanny, Jennene Miller, Meg Harward, Chris Joyce, Josie McKay, Jason Meyer, Rachel Bushell, John Fraser, Jayshree Lavana, Dawn Lockwood, Raymond Marteene, Heidi Buhr, Ruaidhri Carey, Jennifer Coles, Richard Totaro

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. thao.le@monash.edu.
² St. Vincent's Hospital Sydney, University of New South Wales, Sydney, NSW, Australia.
³ Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Anesthesia and Intensive Care, Istituto Mediterraneo Per I Trapianti E Terapie Ad Alta Specializzazione (IRCCS-ISMETT), Palermo, Italy.
⁵ Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
⁶ Clinical Division of General Anaesthesia and Intensive Care, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria.
⁷ Department of Emergency Medicine, Medical Center-University of Freiburg, Medical Faculty-University of Freiburg, Freiburg, Germany.
⁸ Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁹ ASPIRE Trials Program, Division of Pulmonary, Critical Care, and Sleep Medicine, New York University, New York, NY, USA.
¹⁰ Division of Cardiothoracic and Vascular Surgery, College of Physicians and Surgeons, NewYork-Presbyterian Hospital, Columbia University, New York, USA.
¹¹ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
¹² Guy's and St. Thomas' NHS Foundation Trust, London, UK.
¹³ Royal North Shore Hospital, University of NSW, Sydney, Australia.
¹⁴ Adult Intensive Care Services, The Prince Charles Hospital, Chermside, QLD, Australia.
¹⁵ Intensive Care, Gold Coast University Hospital, Gold Coast, University of Queensland, Brisbane, QLD, Australia.
¹⁶ Intensive Care, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia.
¹⁷ Intensive Care Service, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Camperdown, Australia.
¹⁸ Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District, Sydney, Australia.
¹⁹ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
²⁰ University of Sydney, Camperdown, Australia.
²¹ School of Medicine, University of Queensland, Brisbane, QLD, Australia.
²² Department of Intensive Care, The Alfred Hospital, Melbourne, Australia.
²³ Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
²⁴ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
²⁵ Department of Haematology, Monash Health, Melbourne, Australia.

PMID: 40826421
PMCID: PMC12359932
DOI: 10.1186/s13054-025-05606-1

Observational Study

Liberal or restrictive transfusion for veno-arterial extracorporeal membrane oxygenation patients: a target trial emulation using the OBLEX study data

Le Thi Phuong Thao et al. Crit Care. 2025.

. 2025 Aug 18;29(1):360.

doi: 10.1186/s13054-025-05606-1.

Authors

Collaborators

International ECMO Network (ECMONet):
Aidan Burrell, Annalie Jones, Emma Martin, Phoebe McCracken, Jayne Sheldrake, Shirley Vallance, Meredith Young, Dee Figures, Maimoonbe Gough, Maree Houbert, James McCullough, Julie Pitman, Mandy Tallott, Danielle Austin, Peter McCanny, Jennene Miller, Meg Harward, Chris Joyce, Josie McKay, Jason Meyer, Rachel Bushell, John Fraser, Jayshree Lavana, Dawn Lockwood, Raymond Marteene, Heidi Buhr, Ruaidhri Carey, Jennifer Coles, Richard Totaro

Affiliations

¹ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. thao.le@monash.edu.
² St. Vincent's Hospital Sydney, University of New South Wales, Sydney, NSW, Australia.
³ Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Anesthesia and Intensive Care, Istituto Mediterraneo Per I Trapianti E Terapie Ad Alta Specializzazione (IRCCS-ISMETT), Palermo, Italy.
⁵ Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
⁶ Clinical Division of General Anaesthesia and Intensive Care, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria.
⁷ Department of Emergency Medicine, Medical Center-University of Freiburg, Medical Faculty-University of Freiburg, Freiburg, Germany.
⁸ Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁹ ASPIRE Trials Program, Division of Pulmonary, Critical Care, and Sleep Medicine, New York University, New York, NY, USA.
¹⁰ Division of Cardiothoracic and Vascular Surgery, College of Physicians and Surgeons, NewYork-Presbyterian Hospital, Columbia University, New York, USA.
¹¹ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
¹² Guy's and St. Thomas' NHS Foundation Trust, London, UK.
¹³ Royal North Shore Hospital, University of NSW, Sydney, Australia.
¹⁴ Adult Intensive Care Services, The Prince Charles Hospital, Chermside, QLD, Australia.
¹⁵ Intensive Care, Gold Coast University Hospital, Gold Coast, University of Queensland, Brisbane, QLD, Australia.
¹⁶ Intensive Care, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia.
¹⁷ Intensive Care Service, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Camperdown, Australia.
¹⁸ Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District, Sydney, Australia.
¹⁹ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
²⁰ University of Sydney, Camperdown, Australia.
²¹ School of Medicine, University of Queensland, Brisbane, QLD, Australia.
²² Department of Intensive Care, The Alfred Hospital, Melbourne, Australia.
²³ Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
²⁴ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
²⁵ Department of Haematology, Monash Health, Melbourne, Australia.

PMID: 40826421
PMCID: PMC12359932
DOI: 10.1186/s13054-025-05606-1

Abstract

Background: The optimal transfusion threshold for patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains uncertain.

Methods: We used data from OBLEX (ClinicalTrials.gov: NCT03714048), an international, prospective, observational study conducted across 12 centres in Australia, Europe, and North America between 2019 and 2022. The study collected information on patient demographics, bleeding risk factors, transfusion practices during the first seven days of ECMO, and in-hospital mortality. Using these data, we emulated a target trial comparing the effects of liberal transfusion practice (transfusion initiated at Hb ≥ 90 g/L) and restrictive transfusion practice (transfusion initiated at Hb ≤ 70 g/L) on hospital mortality within seven days of ECMO initiation. Sequential trials approach was used to estimate the causal contrast.

Results: A total of 534 patients were included, with 46% dying during hospitalisation. After accounting for potential confounders, the liberal transfusion practice demonstrated a modest survival benefit within the first two days of ECMO, with differences in survival probabilities of 12% (95% CI 3% to 21%) at day 2 and 13% (95% CI 2% to 25%) at day 3, corresponding to the number needed to treat (NNT) of 8 and 7 respectively. No differences in survival benefit were found after day 3. These results were consistent across sensitivity and exploratory analyses.

Conclusion: This target trial emulation study suggests that a liberal transfusion threshold may provide a modest survival benefit during the early course of VA-ECMO, but no benefit afterwards. Prospective studies are needed to confirm these findings, assess clinical adoption, and investigate underlying mechanism.

Keywords: ECMO; Target trial emulation; Transfusion threshold; VA ECMO.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethics approval was obtained in Australia (HREC/18/SVH/202), which granted a waiver of consent. Non-Australian centres were required to apply for local approval based on their legal requirements. Consent for publication: Not appliable. Competing interests: The authors declare no competing interests.

Figures

**Fig. 1**
A) Transfusion pattern in the OBLEX study B) Number of patients in each arm and follow-up times in the combined sequential trials. Each line represents one patient and their corresponding follow-up duration

**Fig. 2**
A) Estimated survival curves of the liberal and restrictive transfusion strategies, B) Estimated survival difference between the liberal and restrictive transfusion strategies. The shaded areas show the 95% confidence intervals

See this image and copyright information in PMC

References

1. Lindstrom SJ, Pellegrino VA, Butt WW. Extracorporeal membrane oxygenation. Med J Aust. 2009;191(3):178–82. - PubMed
1. Guimbretière G, Anselmi A, Roisne A, Lelong B, Corbineau H, Langanay T, et al. Prognostic impact of blood product transfusion in VA and VV ECMO. Perfusion. 2019;34(3):246–53. - PubMed
1. Raasveld SJ, Karami M, Schenk J, Dos Reis Miranda D, Mandigers L, Dauwe DF, et al. Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: a multicenter retrospective observational cohort study. Transfusion (Paris). 2023;63(10):1809–20. - PubMed
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1. Blet A, McNeil JB, Josse J, Cholley B, Cinotti R, Cotter G, et al. Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors. Crit Care. 2022;7(26):307. - PMC - PubMed

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Liberal or restrictive transfusion for veno-arterial extracorporeal membrane oxygenation patients: a target trial emulation using the OBLEX study data

Collaborators

Affiliations

Liberal or restrictive transfusion for veno-arterial extracorporeal membrane oxygenation patients: a target trial emulation using the OBLEX study data

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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References

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