Julien Pottecher1, Anne-Claude Roche, Tristan Dégot, Olivier Helms, Jean-Gustave Hentz, Jean-Paul Schmitt, Pierre-Emmanuel Falcoz, Nicola Santelmo, François Levy, Olivier Collange, Béatrice Uring-Lambert, Siamak Bahram, Mickaël Schaeffer, Nicolas Meyer, Bernard Geny, Philippe Lassalle, Pierre Diemunsch, Gilbert Massard, Romain Kessler, Annick Steib. 1. 1 Hôpitaux Universitaires de Strasbourg, Pôle d'Anesthésie-Réanimation SAMU-SMUR, Service d'Anesthésie-Réanimaton Chirurgicale, Hôpital de Hautepierre, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Physiologie, Strasbourg, France. 2 Hôpitaux Universitaires de Strasbourg, Pôle d'Anesthésie-Réanimation SAMU-SMUR, Service d'Anesthésie-Réanimations Chirurgicales, Nouvel Hôpital Civil, Strasbourg, France. 3 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Pneumologie, Nouvel Hôpital Civil, Strasbourg, France. 4 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Chirurgie Thoracique, Nouvel Hôpital Civil, Strasbourg, France. 5 Hôpitaux Universitaires de Strasbourg, Pôle de Biologie, Laboratoire Central d'Immunologie, Nouvel Hôpital Civil, Strasbourg, France. 6 Laboratoire d'ImmunoRhumatologie Moléculaire, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, France. 7 Hôpitaux Universitaires de Strasbourg, Service de Santé Publique, Groupe Méthode en Recherche Clinique, Strasbourg, France. 8 Université de Strasbourg, Faculté de Médecine, Laboratoire de Biostatistique et Informatique Médicale, EA3430 Progression Tumorale et Microenvironnement. Approches translationnelles et Epidemiologie', LabEx IRMIA, Strasbourg, France. 9 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Physiologie et d'Explorations Fonctionnelles, Nouvel Hôpital Civil, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Physiologie, Strasbourg, France. 10 Institut National de la Santé et de la Recherche Médicale, U1019, Pulmonary Immunity team and Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
Abstract
BACKGROUND: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. METHODS: After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.
BACKGROUND: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. METHODS: After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.
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Authors: Laveena Munshi; Marcelo Cypel; Alaa Mohamed; Alyaa Elhazmi; Eddy Fan; Damon Scales; Jussi Tikkanen; Lorenzo Del Sorbo; Niall D Ferguson; Shaf Keshavjee; John Granton Journal: Transplant Direct Date: 2022-09-26