Déterminants cliniques, physiopathologiques et pronostics associés aux complications liées à l’hémostase au cours des assistances circulatoires de courte durée à pompe centrifuge

The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics.La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...

Clinical, pathophysiological, and prognostic factors associated with hemostasis-related complications during centrifugal pump-based short-term circulatory support

La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...]The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics

Déterminants cliniques, physiopathologiques et pronostics associés aux complications liées à l’hémostase au cours des assistances circulatoires de courte durée à pompe centrifuge

The purpose of this dissertation is to characterize hemostasis-related complications in patients supported by peripheral VA-ECMO to improve their prevention and to optimize the antithrombotic therapeutic approaches in use. In a first study, we qualitatively and quantitatively described the composition of thrombi collected from the VA-ECMO circuits. We observed that these thrombi are mainly made of VWF, fibrin and in a lesser proportion of platelets and RBCs. Our quantitative approach also allowed us to demonstrate the presence of NETs while there was no active septic, confirming the possibility of aseptic NETosis under VA-ECMO. By hierarchical cluster analysis, we identified 2 types of thrombi, each of which may be related to a different mechanism of formation. In this study, the location of thrombi on the VA-ECMO circuit did not impact their compositions, highlighting the heterogeneity of thrombi formed within VA-ECMO and the multifactorial mechanisms that support thrombosis in this setting. In a second study, we compared the performance of surface coatings on VA-ECMO circuits to reduce thrombinoformation and its clinical consequences. Two of the most used coatings in daily practice were compared: the phosphorylcholin-based coating and the polysaccharide-albumin-based coating. We observed a higher rate of thrombotic complications in the phosphorylcholin group without any excess bleeding events or mortality in either group. In addition, compared with thrombi from phosphorylcholin-coated circuit junctions, those from polysaccharide-albumin-coated circuits were poorer in VWF. Our work suggests that the level of anticoagulation should be modulated according to the type of coating of the ECMO circuit.The aim of our third study was to identify the most relevant bleeding events that may guide clinical decision-making for more aggressive clinical management and a greater investment in research. To this end, we compared the association between 3 bleeding classifications with 28-day mortality. The ELSO definition already in use and the BARC classification classes ≥ type 2 were associated with 28-day mortality and thus retained as definitions of major bleeding. Laboratory parameters that are predictors major bleeding according to the ELSO definition were decreased fibrinogen, platelet count, and hemoglobin at cannulations. Body mass index and postcardiotomy etiology were also predictive of ELSO major bleeding. In an additional work related to the topic of the thesis, we studied two of the most used laboratory tests for the monitoring of systemic heparin during VA-ECMO, the APTT and the Anti-Xa activity, to identify the most relevant. First, we studied the relationship between these two tests and then analyzed in a second objective the impact of biological influencing factors on this relationship. Next, we determined their associations with thrombotic and hemorrhagic complications. Although linearly associated, the rate of discordance between their measurements was 39 % for an Anti-Xa reference range of 0.3 - 0.7 IU/mL. Neither APTT nor Anti-Xa was associated with thrombotic or bleeding complications. Taken together, our results highlight the heterogeneity of thrombi from peripheral VA-ECMO, the involvement of numerous causal factors that underline thrombotic and hemorrhagic complications, both not predictable by routine tests. Finally, our work underscored the need for new approaches in thrombotic or hemorrhagic complications management with targets set at an individual level considering both patient and ECMO circuit characteristics.La problématique de cette thèse est la caractérisation des complications liées à l’hémostase chez le patient assisté par ECMO-VA périphérique afin d’en améliorer la prévention et de rationaliser les approches antithrombotiques en usage. Dans une première étude, nous avons décrit qualitativement et quantitativement la composition des thrombi formés sur les circuits d’ECMO-VA. Nous avons observé que ces thrombi sont majoritairement composés de VWF, de fibrine et dans une moindre proportion de plaquettes et d’érythrocytes. Notre approche quantitative a également permis de mettre en évidence la présence de NETs en l’absence de toute pathologie septique active, confirmant la possibilité d’une NETose aseptique sous ECMO-VA. Par une analyse en cluster hiérarchique, nous avons identifié 2 types de thrombi pouvant relever chacun d’un mécanisme de formation différent. Dans cette étude, la localisation des thrombi sur le circuit d’ECMO-VA n’impactait pas leurs compositions, ce qui souligne l’hétérogénéité des thrombi formés sous ECMO-VA et la multiplicité des mécanismes à l’origine de la thrombinoformation dans ce contexte. Dans un second travail, nous avons comparé la performance des revêtements de surfaces des circuits d’ECMO-VA à réduire la thrombinoforation et ses conséquences cliniques. Deux des revêtements les plus utilisés en routine étaient comparés : celle à base de phosphorylcholine et à base d’héparine. Nous avons observé un taux de complications thrombotiques plus conséquent dans le groupe phosphorylcholine sans surrisque hémorragique ou de mortalité dans les deux groupes. Par ailleurs, comparativement aux thrombi issus des jonctions de circuits traités par revêtement de phosphorylcholine, ceux provenant de circuits traités par polysaccharide-albumine étaient plus pauvres en VWF. Notre travail suggère que l’intensité de l’anticoagulation devrait être modulée en fonction du type de revêtement de surface du circuit d’ECMO. Notre troisième étude avait pour but d’identifier les saignements les plus graves justifiants d’une prise en charge clinique agressive et d’un investissement plus conséquent en recherche. À cette fin, nous avons comparé l’association entre 3 classifications de saignement avec la mortalité à 28 jours. La définition ELSO déjà en usage et les classes de la classification BARC ≥ type 2 étaient associées à la mortalité et retenues donc comme définitions de l’hémorragie majeure. Les facteurs biologiques prédictifs de l’hémorragie grave d’après la définition de l’ELSO étaient la baisse du fibrinogène, du compte plaquettaire et de l’hémoglobine à la canulation. L’indice de masse corporelle et l’étiologie postcardiotomie étaient également prédictifs de la survenue de cette complication. Dans un travail additionnel portant sur la thématique de la thèse, nous avons étudié deux des tests les plus utilisés pour la surveillance de l’héparinothérapie systémique sous ECMO, le TCA et l’activité Anti-Xa afin d’identifier le plus pertinent. Pour ce faire, dans un premier objectif nous avons étudié la relation entre ces deux tests puis avons analysé dans un second objectif l’impact de facteurs biologiques d’influences sur cette relation. Ensuite, nous avons déterminé leurs associations avec les complications thrombotiques et hémorragiques. Bien qu’étant linéairement associé, le taux de discordance entre leurs mesures était de 39 % pour une fenêtre référence d’Anti-Xa de 0,3 — 0,7 UI/mL. Ni le TCA et ni l’Anti-Xa n’étaient associées aux complications thrombotiques ou hémorragiques [...

Development and usage of an anesthesia data warehouse: lessons learnt from a 10-year project

International audienceAbstract This paper describes the development and implementation of an anesthesia data warehouse in the Lille University Hospital. We share the lessons learned from a ten-year project and provide guidance for the implementation of such a project. Our clinical data warehouse is mainly fed with data collected by the anesthesia information management system and hospital discharge reports. The data warehouse stores historical and accurate data with an accuracy level of the day for administrative data, and of the second for monitoring data. Datamarts complete the architecture and provide secondary computed data and indicators, in order to execute queries faster and easily. Between 2010 and 2021, 636 784 anesthesia records were integrated for 353 152 patients. We reported the main concerns and barriers during the development of this project and we provided 8 tips to handle them. We have implemented our data warehouse into the OMOP common data model as a complementary downstream data model. The next step of the project will be to disseminate the use of the OMOP data model for anesthesia and critical care, and drive the trend towards federated learning to enhance collaborations and multicenter studies

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: discussion about potential confounding factors

International audienc

C-reactive protein kinetics after major surgery

BACKGROUND: Diagnosis of sepsis in the postoperative period is a challenge. Measurements of inflammatory markers, such as C-reactive protein (CRP), have been proposed in medical patients, but the interpretation of these values in surgical patients is more difficult. We evaluated the changes in blood CRP levels and white blood cell count in postoperative patients with and without infection. METHODS: All patients admitted to our 34-bed Department of Intensive Care after major (elective or emergency) cardiac, neuro-, vascular, thoracic, or abdominal surgery during a 4-month period were prospectively included. Patients were screened daily and characterized as infected or noninfected. CRP levels and white blood cell counts were recorded daily in all patients for up to 7 days after the surgical intervention. RESULTS: Of the 151 patients enrolled, 115 underwent elective surgery and 36 emergency surgery; cardiac surgery was performed in 49 patients, neurosurgery in 65, abdominal surgery in 25, vascular surgery in 7, and thoracic surgery in 5. In noninfected patients (n = 117), mean CRP values increased from baseline to postoperative day (POD) 3 (P 100 mg/L, suggest the presence of a postoperative infection. © 2014 International Anesthesia Research Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hybrid closure of ventricular septal defect and implantation of systemic right ventricular assist device

Abstract A 50‐year‐old female patient was readmitted with refractory systemic right ventricular failure. The patient underwent a Mustard procedure during childhood for transposition of the great arteries. A significant residual ventricular septal defect was present, which represents a major risk factor of death following ventricular assist device. We describe the combination of ventricular assist device implantation preceded by hybrid closure of ventricular septal defect

Non-steroidal anti-inflammatory drugs use in cardiac surgery: A survey of practices and new insights for future studies

International audienc

Transforming Anesthesia Data Into the Observational Medical Outcomes Partnership Common Data Model: Development and Usability Study

BackgroundElectronic health records (EHRs, such as those created by an anesthesia management system) generate a large amount of data that can notably be reused for clinical audits and scientific research. The sharing of these data and tools is generally affected by the lack of system interoperability. To overcome these issues, Observational Health Data Sciences and Informatics (OHDSI) developed the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to standardize EHR data and promote large-scale observational and longitudinal research. Anesthesia data have not previously been mapped into the OMOP CDM. ObjectiveThe primary objective was to transform anesthesia data into the OMOP CDM. The secondary objective was to provide vocabularies, queries, and dashboards that might promote the exploitation and sharing of anesthesia data through the CDM. MethodsUsing our local anesthesia data warehouse, a group of 5 experts from 5 different medical centers identified local concepts related to anesthesia. The concepts were then matched with standard concepts in the OHDSI vocabularies. We performed structural mapping between the design of our local anesthesia data warehouse and the OMOP CDM tables and fields. To validate the implementation of anesthesia data into the OMOP CDM, we developed a set of queries and dashboards. ResultsWe identified 522 concepts related to anesthesia care. They were classified as demographics, units, measurements, operating room steps, drugs, periods of interest, and features. After semantic mapping, 353 (67.7%) of these anesthesia concepts were mapped to OHDSI concepts. Further, 169 (32.3%) concepts related to periods and features were added to the OHDSI vocabularies. Then, 8 OMOP CDM tables were implemented with anesthesia data and 2 new tables (EPISODE and FEATURE) were added to store secondarily computed data. We integrated data from 5,72,609 operations and provided the code for a set of 8 queries and 4 dashboards related to anesthesia care. ConclusionsGeneric data concerning demographics, drugs, units, measurements, and operating room steps were already available in OHDSI vocabularies. However, most of the intraoperative concepts (the duration of specific steps, an episode of hypotension, etc) were not present in OHDSI vocabularies. The OMOP mapping provided here enables anesthesia data reuse

Evaluation of endothelial damage in sepsis-related ARDS using circulating endothelial cells

Purpose: Endothelial cell activation and dysfunction are involved in the pathophysiology of ARDS. Circulating endothelial cells (CECs) may be a useful marker of endothelial dysfunction and damage but have been poorly studied in ARDS. We hypothesized that the CEC count may be elevated in patients with sepsis-related ARDS compared to those with sepsis without ARDS.SCOPUS: ar.jinfo:eu-repo/semantics/publishe