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Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

OBJECTIVES: To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs). DESIGN: Pooled individual data analysis from five original observational cohort studies. SETTING: European extracorporeal membrane oxygenation (ECMO) centers. PATIENTS: Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87-0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66-3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038). CONCLUSIONS: In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.

Background: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. Methods: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to “conventional” ECMO management (Supine group) in patients with severe ARDS. Results: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42–1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). Conclusions: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.