Mouhamed Djahoum Moussa

Background: Low intraoperative end-tidal carbon dioxide (ET co ₂ ) has been associated with increased postoperative mortality in retrospective studies. However, whether this association is independent of intraoperative hypotension, a strong predictor of mortality, and minute ventilation, a primary determinant of ET co ₂ , remains uncertain. The authors hypothesized that low intraoperative ET co ₂ is independently associated with postoperative mortality after adjustment for both intraoperative hypotension and minute ventilation. Methods: The authors conducted a retrospective cohort study of adults undergoing noncardiac surgery during general anesthesia with mechanical ventilation between 2010 and 2020 at a tertiary care center. Primary exposures were intraoperative mean ET co ₂ , minute ventilation, and hypotension (severity and duration). The primary outcome was in-hospital mortality. Multivariable logistic regression estimated the independent association between ET co ₂ and mortality after adjustment for predefined confounders. An interaction between ET co ₂ and hypotension was tested. Results: Among 185,455 patients (in-hospital mortality, 0.85%), lower intraoperative ET co ₂ was nonlinearly associated with increased mortality (adjusted odds ratio per 5-mmHg decrease from the median, 1.63; 95% CI, 1.36 to 1.86) independent of minute ventilation and hypotension. No significant interaction was observed between ET co ₂ and hypotension ( P = 0.19). Findings were robust across sensitivity analyses. Conclusions: In this large retrospective cohort, low intraoperative ET co ₂ was independently associated with increased in-hospital mortality, irrespective of intraoperative hypotension and minute ventilation. These results suggest that ET co ₂ provides prognostic information beyond arterial pressure alone and may be a valuable marker for postoperative risk stratification.

Background: Post‐myocardial infarction ventricular septal defect (VSD) is a rare but highly lethal complication of acute myocardial infarction. In cases of extensive septal destruction, surgical reconstruction is often not feasible. We report the first clinical experience with implantation of the Aeson total artificial heart (TAH) in patients with irreparable post‐infarction VSD. Methods: This multicenter retrospective analysis included 10 male patients with severe cardiogenic shock who underwent Aeson TAH implantation at four centers in Germany and France between November 2022 and March 2025. All patients required temporary mechanical circulatory support before implantation. Previous surgical VSD repair had failed in four patients, while six were considered unsuitable for surgical reconstruction because of extensive basal septal defects involving the atrioventricular valve apparatus. Results: Following TAH implantation, early extubation was achieved in most patients, whereas three required temporary veno‐venous extracorporeal membrane oxygenation support. No cases of permanent renal failure, irreversible hepatic dysfunction, or neurological complications such as stroke were observed. Eight patients (80%) were successfully bridged to heart transplantation after a median support duration of 167 days, while one patient remains on ongoing device support. During a median follow‐up of 351 days (interquartile range, 202–470 days), four patients died. Overall survival was 80% at 6 months and 60% at 1 year after implantation. Conclusions: Aeson TAH implantation appears to be a feasible bridge‐to‐transplant strategy for selected patients with irreparable post‐myocardial infarction VSD. The procedure provided hemodynamic stabilization, facilitated recovery of end‐organ function, and resulted in favorable short‐ to mid‐term outcomes in an otherwise fatal clinical condition.

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

Objectives: Comparisons of preload unloading techniques for left ventricle overdistension during venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support are scarce. We compared outcomes in patients with left ventricular distension treated with cannulated percutaneous atrioseptostomy combined with ECMO—specified as selective biatrial extracorporeal membrane oxygenation (SBA‐ECMO)—versus those treated with Impella CP/5.0 in combination with ECMO (ECPELLA). Methods: Consecutive adult patients who received VA‐ECMO and underwent additional left ventricle unloading between January 2014 and March 2023 were studied. The primary endpoint was the number of ventilation‐free days. The secondary endpoints were serious bleeding, blood product consumption, thrombotic complications, and 28‐day mortality. Results: We included 57 patients, 27 of whom received SBA‐ECMO and 30 of whom received ECPELLA. The median number of ventilation‐free days was 10 days (0–23) with SBA‐ECMO and 5 days (0–23) with the ECPELLA ( p = 0.61). According to the multivariable analyses, SBA‐ECMO was associated with a lower risk of serious bleeding (HR 0.31 [95% CI 0.12–0.80]) and less blood product consumption (RR 0.57 [95% CI 0.36–0.90]) than ECPELLA. Thrombotic complications and 28‐day mortality were similar between the groups before and after multivariable analyses. Conclusions: In patients with left ventricle congestion during VA‐ECMO support, left ventricle unloading with SBA‐ECMO was associated with reduced serious bleeding and transfusions compared with ECPELLA, despite a similar number of ventilation‐free days, thrombotic complications, and mortality. Trial Registration: ClinicalTrials.gov identifiers: NCT03431467 and NCT05577195

Background. Unfractionated heparin is administered in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Anticoagulation monitoring is recommended, with an anti-activated factor X (anti-Xa) targeting 0.3 to 0.7 IU/mL. Owing to heparin’s heterogeneous pharmacokinetic properties, anti-Xa is unpredictable, generating a challenge in anticoagulation practices. The aim of this study was to build a pharmacokinetic model of heparin accounting for potential confounders, and derive an optimized dosing regimen for a given anti-Xa target. Methods. Adult patients undergoing VA-ECMO were included between January 2020 and June 2021. Anticoagulation was managed with an initial 100 IU/kg heparin loading dose followed by a continuous infusion targeting 0.2 to 0.7 IU/mL anti-Xa. The data were split into model development and model validation cohorts. Statistical analysis was performed using a nonlinear mixed effects modeling population approach. Model-based simulations were performed to develop an optimized dosing regimen targeting the desired anti-Xa. Results. A total of 74 patients were included, with 1703 anti-Xa observations. A single-compartment model best fitted the data. Interpatient variability for distribution volume was best explained by body weight, C-reactive protein and ECMO indication (post-cardiotomy shock or medical cardiogenic shock), and interpatient variability for elimination clearance was best explained by serum creatinine and C-reactive protein. Simulations using the optimized regimen according to these covariates showed accurate anti-Xa target attainment. Conclusion. In adult patients on VA-ECMO, heparin’s effect increased with serum creatinine and medical indication, whereas it decreased with body weight and systemic inflammation. We propose an optimized dosing regimen accounting for key covariates, capable of accurately predicting a given anti-Xa target.

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.