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Definitions of major bleeding for predicting mortality in critically ill adult patients who survived 24 hours while supported with peripheral veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: a comparative historical cohort study

Définitions de l’hémorragie majeure pour prédire la mortalité chez la patientèle adulte gravement malade ayant survécu 24 heures sous oxygénation par membrane extracorporelle veino-artérielle périphérique pour un choc cardiogénique : une étude de cohorte historique comparative

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Abstract

Purpose

The severity of bleeding events is heterogeneously defined during peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO). We studied three bleeding definitions in pVA-ECMO: the Extracorporeal Life Support Organization (ELSO)-serious bleeding, the Bleeding Academic Research Consortium (BARC), and the universal definition of postoperative bleeding (UPDB) classifications.

Methods

We included consecutive adult patients supported by pVA-ECMO for refractory cardiogenic shock admitted to Lille academic hospitals between January 2013 and December 2019. We assessed the association of bleeding definitions with the primary endpoint of 28-day all-cause mortality with the use of multivariate models accounting for time-dependent and competing variables. We compared models’ performances using the Harrell’s C-Index and the Akaike information criteria.

Results

Twenty-eight-day mortality occurred in 128/308 (42%) 308 patients. The ELSO-serious bleeding (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.09 to 2.56) and BARC ≥ type 2 (HR, 1.55; 95% CI, 1.01 to 2.37) were associated with 28-day mortality (Harrell’s C-index, 0.69; 95% CI, 0.63 to 0.74 for both). Predictors of ELSO-serious bleeding were postcardiotomy, body mass index, baseline platelets count, fibrinogen, and hemoglobin levels.

Conclusion

Extracorporeal Life Support Organization-serious bleeding and BARC ≥ type 2 are relevant definitions of major bleeding regarding their association with mortality in critically ill patients who survived the first 24 hr while supported with pVA-ECMO for cardiogenic shock.

Study registration

CERAR (IRB 00010254-2022-050, Paris, France); first submitted on 18 April 2022.

Résumé

Objectif

La gravité des événements hémorragiques est définie de manière hétérogène pendant une oxygénation par membrane extracorporelle veino-artérielle périphérique (ECMO-VA périphérique). Nous avons étudié trois définitions du saignement sous ECMO-VA périphérique : les classifications des saignements graves selon l’Extracorporeal Life Support Organization (ELSO), celles du Bleeding Academic Research Consortium (BARC) et la définition universelle du saignement postopératoire (UPDB).

Méthode

Nous avons inclus des patient·es adultes pris·es en charge de manière consécutive par ECMO-VA périphérique à la suite d’un choc cardiogénique réfractaire et admis·es dans les centres hospitaliers universitaires de Lille entre janvier 2013 et décembre 2019. Nous avons évalué l’association des définitions du saignement avec le critère d’évaluation principal de mortalité toutes causes confondues à 28 jours à l’aide de modèles multivariés tenant compte des variables dépendantes du temps et concurrentes. Nous avons comparé les performances des modèles à l’aide de l’indice C de Harrell et du critère d’information d’Akaike.

Résultats

La mortalité à 28 jours est survenue chez 128/308 (42 %) patient·es. Le saignement grave selon l’ELSO (rapport de risque [RR], 1,67; intervalle de confiance [IC] à 95 %, 1,09 à 2,56) et une classification BARC ≥ type 2 (RR, 1,55; IC 95 %, 1,01 à 2,37) étaient associés à une mortalité à 28 jours (indice C de Harrell, 0,69; IC 95 %, 0,63 à 0,74 pour les deux). Les prédicteurs d’hémorragie grave selon l’ELSO étaient la postcardiotomie, l’indice de masse corporelle, la numération plaquettaire initiale, le taux de fibrinogène et les taux d’hémoglobine.

Conclusion

Les définitions du saignement grave de l’Extracorporeal Life Support Organization et une classification BARC ≥ type 2 sont des définitions pertinentes des saignements majeurs en ce qui touche à leur association avec la mortalité chez les personnes gravement malades qui ont survécu aux premières 24 heures alors qu’elles étaient prises en charge par ECMO-VA périphérique à la suite d’un choc cardiogénique.

Enregistrement de l’étude

CERAR (IRB 00010254-2022-050, Paris, France); soumis pour la première fois le 18 avril 2022.

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Author contributions

Mouhamed D. Moussa, André Vincentelli, and Emmanuel Robin contributed to study design and conception. Antoine Lamer, Lise Thellier, Mouhamed D. Moussa, Oliver Lukowiak, Natacha Rousse, Antoine Rauch, Valentin Loobuyck, Guillaume Leroy, Thibault Duburcq, Guillaume Gantois, Xavier Leroy, and Guillaume Schurtz, Slimane Ait-Ouarab contributed to data collection and endpoint adjudication. Julien Labreuche and Antoine Lamer contributed to statistical analyses and data management. Mouhamed D. Moussa, Oliver Lukowiak, Natacha Rousse, Antoine Rauch, Guillaume Schurtz, Valentin Loobuyck, Guillaume Leroy, Slimane Ait-Ouarab, Thibault Duburcq, Guillaume Gantois, Francis Juthier, Christophe Muller, Sophie Susen, Emmanuel Robin, and André Vincentelli contributed to results analysis and interpretation. Mouhamed D. Moussa, Jérôme Soquet, Emmanuel Robin, Oliver Lukowiak, Lise Thellier, and André Vincentelli contributed to drafting the manuscript. All authors contributed to reviewing the manuscript.

Acknowledgements

We are grateful to all the contributors of the Lille Refractory Cardiogenic Shock and Circulatory Assist Device (R-CaSCAD) study group (see ESM eAppendix 2) and to all cardioperfusionists of the department of cardiovascular surgery.

Disclosures

All authors declare no conflicting interest.

Funding statement

French National Research Agency (Programme d’Investissement d’Avenir) with the Hospital-University Research in Health program (Recherche Hospitalo-Universitaire, WILL-ASSIST HEART ANR-17-RHUS-0011).

Data availability

The data sets analyzed during the current study are available from the corresponding author on reasonable request with restriction according to French and EU regulations.

Editorial responsibility

This submission was handled by Dr. Alexis F. Turgeon, Associate Editor, Canadian Journal of Anesthesia/Journal canadien d’anesthésie.

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Authors and Affiliations

  1. Institut Pasteur de Lille, Université de Lille, Inserm, CHU Lille, Lille, France

    Mouhamed D. Moussa MD, PhD, Jérôme Soquet MD, MSc, Emmanuel Robin MD, PhD, Natacha Rousse MD, Antoine Rauch MD, PhD, Valentin Loobuyck MD, MSc, Guillaume Schurtz MD, Francis Juthier MD, PhD, Sophie Susen MD, PhD & André Vincentelli MD, PhD

  2. Pôle d’Anesthésie-Réanimation, CHU Lille, Lille, France

    Mouhamed D. Moussa MD, PhD, Emmanuel Robin MD, PhD, Guillaume Leroy MD, MSc, Guillaume Gantois MD, Xavier Leroy MD, Slimane Ait-Ouarab MD, Antoine Lamer PhD, Lise Thellier MD, MSc, Oliver Lukowiak MD & Christophe Muller MD

  3. Department of Cardiac Surgery, CHU Lille, Lille, France

    Jérôme Soquet MD, MSc, Natacha Rousse MD, Valentin Loobuyck MD, MSc, Francis Juthier MD, PhD & André Vincentelli MD, PhD

  4. Department of Biostatistics, CHU Lille, Lille, France

    Julien Labreuche MSc

  5. Medical Intensive Care Unit, CHU Lille, Lille, France

    Thibault Duburcq MD

  6. Department of Cardiology, CHU Lille, Lille, France

    Guillaume Schurtz MD

  7. Service d’Anesthésie-Réanimation Cardiovasculaire et thoracique, Institut Cœur - Poumon, CHU Lille, 2 avenue Oscar Lambret, 59 037, Lille, France

    Mouhamed D. Moussa MD, PhD

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  1. Mouhamed D. Moussa MD, PhD
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Correspondence to Mouhamed D. Moussa MD, PhD.

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Moussa, M.D., Soquet, J., Robin, E. et al. Definitions of major bleeding for predicting mortality in critically ill adult patients who survived 24 hours while supported with peripheral veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: a comparative historical cohort study. Can J Anesth/J Can Anesth 71, 523–534 (2024). https://doi.org/10.1007/s12630-024-02704-6

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