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Abstract Background Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources.

Abstract Background Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). Methods Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. Results Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p

Abstract Background Although rarely addressed in the literature, a key question in the care of critically pregnant women with severe acute respiratory distress syndrome (ARDS), especially at the time of extracorporeal membrane oxygenation (ECMO) decision, is whether delivery might substantially improve the mother’s and child’s conditions. This multicenter, retrospective cohort aims to report maternal and fetal short- and long-term outcomes of pregnant women with ECMO-rescued severe ARDS according to the timing of the delivery decision taken before or after ECMO cannulation. Methods We included critically ill women with ongoing pregnancy or within 15 days after a maternal/child-rescue-aimed delivery supported by ECMO for a severe ARDS between October 2009 and August 2021 in four ECMO centers. Clinical characteristics, critical care management, complications, and hospital discharge status for both mothers and children were collected. Long-term outcomes and premature birth complications were assessed. Results Among 563 women on venovenous ECMO during the study period, 11 were cannulated during an ongoing pregnancy at a median (range) of 25 (21–29) gestational weeks, and 13 after an emergency delivery performed at 32 (17–39) weeks of gestation. Pre-ECMO PaO2/FiO2 ratio was 57 (26–98) and did not differ between the two groups. Patients on ECMO after delivery reported more major bleeding (46 vs. 18%, p = 0.05) than those with ongoing pregnancy. Overall, the maternal hospital survival was 88%, which was not different between the two groups. Four (36%) of pregnant women had a spontaneous expulsion on ECMO, and fetal survival was higher when ECMO was set after delivery (92% vs. 55%, p = 0.03). Among newborns alive, no severe preterm morbidity or long-term sequelae were reported. Conclusion Continuation of the pregnancy on ECMO support carries a significant risk of fetal death while improving prematurity-related morbidity in alive newborns with no difference in maternal outcomes. Decisions regarding timing, place, and mode of delivery should be taken and regularly (re)assess by a multidisciplinary team in experienced ECMO centers.

Abstract Background Augmented renal clearance (ARC) remains poorly evaluated in ICU. The objective of this study is to provide a full description of ARC in ICU including prevalence, evolution profile, risk factors and outcomes. Methods This was a retrospective, single-center, observational study. All the patients older than 18 years admitted for the first time in Medical ICU, Bichat, University Hospital, APHP, France, between January 1, 2017, and November 31, 2020 and included into the Outcomerea database with an ICU length of stay longer than 72 h were included. Patients with chronic kidney disease were excluded. Glomerular filtration rate was estimated each day during ICU stay using the measured creatinine renal clearance (CrCl). Augmented renal clearance (ARC) was defined as a 24 h CrCl greater than 130 ml/min/m2. Results 312 patients were included, with a median age of 62.7 years [51.4; 71.8], 106(31.9%) had chronic cardiovascular disease. The main reason for admission was acute respiratory failure (184(59%)) and 196(62.8%) patients had SARS-COV2. The median value for SAPS II score was 32[24; 42.5]; 146(44%) and 154(46.4%) patients were under vasopressors and invasive mechanical ventilation, respectively. The overall prevalence of ARC was 24.6% with a peak prevalence on Day 5 of ICU stay. The risk factors for the occurrence of ARC were young age and absence of cardiovascular comorbidities. The persistence of ARC during more than 10% of the time spent in ICU was significantly associated with a lower risk of death at Day 30. Conclusion ARC is a frequent phenomenon in the ICU with an increased incidence during the first week of ICU stay. Further studies are needed to assess its impact on patient prognosis.

Abstract Background Extracorporeal membrane oxygenation (ECMO) was frequently used to treat patients with severe coronavirus disease-2019 (COVID-19)-associated acute respiratory distress (ARDS) during the initial outbreak. Care of COVID-19 patients evolved markedly during the second part of 2020. Our objective was to compare the characteristics and outcomes of patients who received ECMO for severe COVID-19 ARDS before or after July 1, 2020. Methods We included consecutive adults diagnosed with COVID-19 in Paris–Sorbonne University Hospital Network ICUs, who received ECMO for severe ARDS until January 28, 2021. Characteristics and survival probabilities over time were estimated during the first and second waves. Pre-ECMO risk factors predicting 90-day mortality were assessed using multivariate Cox regression. Results Characteristics of the 88 and 71 patients admitted, respectively, before and after July 1, 2020, were comparable except for older age, more frequent use of dexamethasone (18% vs. 82%), high-flow nasal oxygenation (19% vs. 82%) and/or non-invasive ventilation (7% vs. 37%) after July 1. Respective estimated probabilities (95% confidence intervals) of 90-day mortality were 36% (27–47%) and 48% (37–60%) during the first and the second periods. After adjusting for confounders, probability of 90-day mortality was significantly higher for patients treated after July 1 (HR 2.27, 95% CI 1.02–5.07). ECMO-related complications did not differ between study periods. Conclusions 90-day mortality of ECMO-supported COVID-19–ARDS patients increased significantly after July 1, 2020, and was no longer comparable to that of non-COVID ECMO-treated patients. Failure of prolonged non-invasive oxygenation strategies before intubation and increased lung damage may partly explain this outcome.

Abstract Kinase inhibitors hold great potential as targeted therapy against malignant cells. Among them, the tyrosine kinase inhibitor dasatinib is known for a number of clinically relevant off-target actions, attributed in part to effects on components of the immune system, especially conventional T-cells and natural killer (NK)-cells. Here, we have hypothesized that dasatinib also influences non-conventional T-αβ cell subsets known for their potential anti-tumoral properties, namely iNKT cells and the distinct new innate CD8 T-cell subset. In mice, where the two subsets were originally characterized, an activated state of iNKT cells associated with a shift toward an iNKT cell Th1-phenotype was observed after dasatinib treatment in vivo. Despite decreased frequency of the total memory CD8 T-cell compartment, the proportion of innate-memory CD8 T-cells and their IFNγ expression in response to an innate-like stimulation increased in response to dasatinib. Lastly, in patients administered with dasatinib for the treatment of BCR-ABL-positive leukemias, we provided the proof of concept that the kinase inhibitor also influences the two innate T-cell subsets in humans, as attested by their increased frequency in the peripheral blood. These data highlight the potential immunostimulatory capacity of dasatinib on innate T-αβ cells, thereby opening new opportunities for chemoimmunotherapy.