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OBJECTIVES The aim of this study was to evaluate the association between vasoactive–inotropic score (VIS), calculated in the 24 h after heart transplantation, and post-transplant mortality and morbidity. METHODS This was an observational single-centre retrospective study. Patients admitted to surgical intensive care unit after transplantation, between January 2015 and December 2018, were reviewed consecutively. VISmax was calculated as dopamine+ dobutamine+ 100 × epinephrine + 100 × norepinephrine + 50 × levosimendan + 10 × milrinone (all in µg/kg/min) + 10 000 × vasopressin (units/kg/min), using the maximum dosing rates of vasoactive and inotropic medications in the 24 h after intensive care unit admission. The primary outcome was mortality at 1 year post-transplant. The secondary outcomes included length of stay, duration of mechanical ventilation and inotropic support and the occurrence of septic shock, ventilator-associated pneumonia, bloodstream infection or renal replacement therapy. RESULTS A total of 151 patients underwent heart transplantation and admitted to intensive care unit. The median VISmax was 39.2 (interquartile range = 19.4–83.0). VISmax was independently associated with 1-year post-transplant mortality, as well as recipient age [hazard ratio (HR) = 1.004, P-value = 0.013], recipient gender (female to male: hazard ratio = 2.23, P-value = 0.047) and combined transplantation (hazard ratio = 2.85, P-value = 0.048). There was a significant association between VISmax and duration of mechanical ventilation (P-value < 0.001), length of stay (P-value = 0.002), duration of infused inotropes (P-value < 0.001), occurrence of bloodstream infections, septic shocks, ventilation-acquired pneumonia and renal replacement therapy. CONCLUSIONS VISmax calculated during the first 24 h after postoperative intensive care unit admission in transplanted patients is independently associated with 1-year mortality. In addition, length of stay, duration of mechanical ventilation and infused inotropes increased with increasing VISmax.

International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

Objectives The authors aimed to identify risk factors associated with prolonged mechanical ventilation (PMV) after scheduled cardiac surgery under cardiopulmonary bypass (CPB). Design A single-center, observational study. Setting Tertiary hospital. Participants All adult patients who underwent scheduled cardiac surgery under cardiopulmonary bypass between January 2017 and December 2017. Interventions None. Measurement and Main Results Among the 568 patients included, 68 (12.0%) presented a PMV. The median ventilation time was 5.7 hours in the group without PMV and 85.2 hours in the group with PMV. A logistic regression found five variables independently associated with the occurrence of PMV: (1) prior cardiac surgery, (2) preoperative congestive heart failure, (3) preoperative creatinine clearance 4 mmol/L on admission. A predictive score to allow the authors to anticipate PMV was developed from the regression coefficient of perioperative factors independently associated with PMV. With a threshold of 2/13, the score had a sensitivity of 80.9%, a specificity of 80.5%, a positive predictive value of 37.2%, and a negative predictive value of 96.7%. The score then was validated in a distinct cohort. Conclusions The study authors have developed a simple score to predict PMV in patients undergoing cardiac surgery with CPB. This score could allow clinicians to identify a high-risk population that might benefit from specific management upon arrival in the intensive care unit.

Resume Le College national des enseignants d’anesthesie et de reanimation (CNEAR) reunit les 181 professionnels hospitalo-universitaires de l’anesthesie-reanimation impliques dans l’enseignement et la recherche en anesthesie, reanimation et medecine perioperatoire. Les objectifs du CNEAR pour la discipline anesthesie-reanimation & medecine peri-operatoire sont avant tout pedagogiques, a destination des etudiants du troisieme et du deuxieme cycle des etudes medicales. Le CNEAR intervient ainsi dans l’organisation, l’evaluation et la validation de l’enseignement du troisieme cycle des specialites medicales. Il realise la publication d’un referentiel actualise de connaissances a destination des etudiants du deuxieme cycle des etudes medicales. Grâce a un partenariat fort avec l’universite numerique en sante et sport (UNESS), le CNEAR assure la mise en ligne de contenus pedagogiques sur la plateforme SIDES NG, la mise en place du livret electronique de l’interne et le suivi regulier du curriculum des internes. Les membres du CNEAR participent egalement a la representation de la discipline aupres des pouvoirs publics et des tutelles au sein du Conseil national professionnel d’anesthesie-reanimation et medecine peri-operatoire (CNP-ARMPO). Pour atteindre ces objectifs, le CNEAR travaille en etroite collaboration avec la sous-section 48-01 (Anesthesie-reanimation et medecine peri-operatoire) du Conseil national des universites et la Societe francaise d’anesthesie et de reanimation (SFAR). Il est par ailleurs membre de droit du CNP-ARMPO et de la Coordination nationale des colleges d’enseignants en medecine (CNCEM) et etend ses collaborations internationales grâce a un partenariat prometteur avec UNESS-International.

Resume La chirurgie cardiaque est une chirurgie a risque proposee chez des patients de plus en plus âges et comorbides. Les scores sont utiles pour predire la mortalite postoperatoire mais peuvent etre mis en defaut pour la prediction du risque individuel. La prise en charge perioperatoire repose sur une evaluation precise des antecedents du patient et du retentissement de sa cardiopathie. Les nouvelles strategies de rehabilitation amelioree apres chirurgie cardiaque sont prometteuses, notamment en ameliorant l’analgesie des patients. La circulation extracorporelle necessaire a la plupart des interventions participe a la physiopathologie de la plupart des complications postoperatoires. Les differentes complications sont liees aux antecedents du patient et a la complexite de la chirurgie. Le developpement des procedures mini-invasives (TAVI notamment) montre des resultats encourageants et permet d’offrir a pratiquement chaque patient une solution adaptee a son etat de base et a sa pathologie.

Background: The current practices regarding the management of antithrombotic therapy during the early postoperative course of cardiac surgery are not well described. Methods: An online survey with multiple-choice questions was sent to cardiac anesthesiologists and intensivists from France. Results: The response rate was 27% (n = 149), with 2/3 of the respondents having less than 10 years of experience. A total of 83% of the respondents reported using an institutional protocol for antithrombotic management. A total of 85% (n = 123) of the respondents regularly used low-molecular-weight heparin (LMWH) during the immediate postoperative course. For 23%, 38%, 9%, and 22% of the physicians, LMWH administration was initiated between the 4th and 6th hour, between the 6th and 12th hour, between the 12th and 24th hour, and on postoperative day 1, respectively. The main reasons for not using LMWH (n = 23) were a perceived increased risk of perioperative bleeding (22%), poor reversal compared with unfractionated heparin (74%), local habits and the refusal of surgeons (57%), and its overly complex management (35%). The modalities of LMWH use were widely varied among the physicians. Chest drains were mostly removed within 3 days of surgery with an unchanged dose of antithrombotic therapy. Regarding temporary epicardial pacing wire removal anticoagulation, 54%, 30%, and 17% of the respondents left the dose unchanged, suspended the anticoagulation, or lowered the anticoagulation dose, respectively. Conclusion: LMWH was inconsistently used after cardiac surgery. Further research is warranted to provide high-quality evidence regarding the benefits and safety of LMWH use early after cardiac surgery.

International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2

Purpose To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. Methods COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. Results From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54–71] years and SAPS II 37 [28–50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10–14) cmH2O, and 24 (21–27) cmH2O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6–34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO2/FiO2 ratio and a shorter time between first symptoms and ICU admission. Conclusion Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients. Electronic supplementary material The online version of this article (10.1007/s00134-020-06294-x) contains supplementary material, which is available to authorized users.

International audience; Objectives: Postcardiotomy cardiogenic shock occurs in 2-6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients.Design: Retrospective observational cohort study between January 2013 and December 2016.Setting: An 18-bed surgical ICU in a university hospital.Patients: A TOTAL OF: A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients.Interventions: None.Measurements and main results: The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3-16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31-6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01-1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02-1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001-1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006-1.018]; p < 0.001) on the day of implantation.Conclusions: Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.

Background Pneumonia is a frequent complication in patients undergoing heart transplantation (HTx) that increases morbidity and mortality in this population. Nevertheless, the risk factors for postoperative pneumonia (POP) are still unknown. The aim of this study was to investigate the predictive risk factors for POP in HTx recipients. Methods In this retrospective study, all patients undergoing HTx between January 2014 and December 2015 were included. All cases of POP occurring until hospital discharge were investigated. The study aimed to determine risk factors using univariate and multivariate Cox regression models. Data are expressed in Odds Ratio [95% CI]. P Results A total of 175 patients were included without any patients being lost to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients. Enterobacteriaceae and Pseudomonas aeruginosa were the most common pathogens. In the multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42 [1.12–1.80], P P P = 0.01) and 1 year (OR: 6.8 [2.5–8.4], P Conclusion After HTx, preoperative mechanical ventilation and blood transfusion were risk factors for POP and were associated with increased mortality. Enterobacteriaceae and Pseudomonas aeruginosa are the most common pathogens of POP.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., i/ the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; ii/ the importance of developing translational research from which therapeutic innovations can emerge; iii/ the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research. Copyright © 2022. Published by Elsevier Masson SAS.

Post-cardiotomy low cardiac output syndrome (PC-LCOS) is a life-threatening complication after cardiac surgery involving a cardiopulmonary bypass (CPB). Mechanical circulatory support with veno-arterial membrane oxygenation (VA-ECMO) may be necessary in the case of refractory shock. The objective of the study was to develop a machine-learning algorithm to predict the need for VA-ECMO implantation in patients with PC-LCOS.Patients were included in the study with moderate to severe PC-LCOS (defined by a vasoactive inotropic score (VIS) 10 with clinical or biological markers of impaired organ perfusion or need for mechanical circulatory support after cardiac surgery) from two university hospitals in Paris, France. The Deep Super Learner, an ensemble machine learning algorithm, was trained to predict VA-ECMO implantation using features readily available at the end of a CPB. Feature importance was estimated using Shapley values.Between January 2016 and December 2019, 285 patients were included in the development dataset and 190 patients in the external validation dataset. The primary outcome, the need for VA-ECMO implantation, occurred respectively, in 16% (n = 46) and 10% (n = 19) in the development and the external validation datasets. The Deep Super Learner algorithm achieved a 0.863 (0.793-0.928) ROC AUC to predict the primary outcome in the external validation dataset. The most important features were the first postoperative arterial lactate value, intraoperative VIS, the absence of angiotensin-converting enzyme treatment, body mass index, and EuroSCORE II.We developed an explainable ensemble machine learning algorithm that could help clinicians predict the risk of deterioration and the need for VA-ECMO implantation in moderate to severe PC-LCOS patients.

Background Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. Methods All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. Results Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96–1.68], p = 0.09 and HR 1.19 [0.998–1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). Conclusions In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity.

BACKGROUND: Hospital-Acquired Pneumonia (HAP) is the most common and severe complication in patients treated with veno-arterial extracorporeal membrane oxygenation (ECMO). HAP early detection is challenging but crucial for improving clinical outcomes. We conduct an observational study to assess whether Lung Ultrasound (LUS) improves detection of HAP in in patients treated with veno-arterial ECMO.METHODS: We conducted a single-center, prospective, observational study including adult patients receiving veno-arterial extracorporeal membrane oxygenation assistance that presented acute respiratory failure. Bedside LUS and chest radiography were performed at the time of inclusion when HAP was suspected. Then the patients were independently assessed for HAP including microbiological evidence. The sonographic features of HAP on veno-arterial ECMO were determined. We then compared the performance of the lung ultrasound simplified clinical pulmonary score (LUS-sCPIS), including bio-clinical data and the Doppler detection of intrapulmonary shunt, to the sCPIS, including bio-clinical and chest radiological data for detection of HAP. RESULTS: We included 70 patients, of which 44 (63%) were independently diagnosed with hospital-acquired pneumonia. LUS examination revealed that Doppler intrapulmonary shunt (P=0.0000043) and dynamic air bronchogram (P=0.00024) were the most frequent hospital-acquired pneumonia-related signs. The LUS-sCPIS (Area under the curve = 0.77) yielded significantly better results than the sCPIS (Area under the curve = 0.65; P = 0.004), while leukocyte count, temperature and chest radiology were not discriminating for the hospital-acquired pneumonia diagnosis.CONCLUSION: The diagnosis of hospital-acquired pneumonia is a daily challenge for the clinician managing patients on veno-arterial ECMO . Lung ultrasound is more powerful than chest radiography and can be a valuable aid as initial imaging modality for the diagnosis of pneumonia. Intrapulmonary shunt detected using color Doppler and dynamic air bronchogram appear to be particularly discriminating for the diagnosis of hospital-acquired pneumonia.CLINICAL TRIAL REGSITRATION: NA

Background Management of the increasing number of sensitized heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitization therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy. Methods A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/- perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (AMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our center. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection, and cardiac allograft vasculopathy-free survival. Results A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500 to 1000 and greater than 1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of antibody-mediated rejection. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells. Conclusions This exclusively posttransplant prophylactic strategy achieved favorable outcomes in heart transplant recipients with pfDSA.

BACKGROUND Although venous thrombosis after venovenous–extracorporeal membrane oxygenation (ECMO) is well described, vascular complications occurring after venoarterial ECMO (VA-ECMO) removal have not yet been thoroughly described. Our aim was to evaluate the frequency of vascular (arterial and venous) complications after VA-ECMO removal and try to identify the risk factors associated with them. METHODS Retrospective analysis of data prospectively collected in 2 intensive care units was performed. Consecutive patients successfully weaned off VA-ECMO during year 1 were screened for cannula-associated deep vein thrombosis (CaDVT) or arterial complications (arterial thrombosis/stenosis) using Doppler ultrasonography . RESULTS From November 2018 to November 2019, a total of 107 patients with a median (interquartile range [IQR]) age of 54 (42–63) years and a median (IQR) ECMO support duration of 8 (2–5) days were successfully weaned off VA-ECMO and included. CaDVT occurred in 44 patients (41%), and arterial complications occurred in 15 (14%) (9 acute leg ischemia , 1 arteriovenous femoral fistula , and 5 late femoral stenosis). Multivariable analysis retained longer duration of ECMO support (odds ratio [OR]: 1.12 per day; 95% CI: 1.02–1.22) and infection occurring on ECMO (OR: 3.03; 95% CI: 1.14–8.03) as independent risk factors for CaDVT, whereas older age (OR: 0.97 per year; 95% CI: 0.94–0.99) and previous anti-coagulation use (OR: 0.21; 95% CI: 0.06–0.68) were protective factors for CaDVT. No risk factors for arterial complications were identified. CONCLUSIONS In patients requiring VA-ECMO support, vascular complications occurred frequently after its removal, especially CaDVT. Arterial complications, either early leg ischemia or late arterial stenosis , were observed less often. Strategies aimed at preventing CaDVT after VA-ECMO remain to be determined.

BackgroundThe COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU).MethodsCharacteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality.ResultsThe analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27;p ConclusionPatients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission.

The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of Candida parapsilosis isolates harboring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understand the epidemiology, pathogenicity, and transmission of resistant Candida parapsilosis. Faced with an outbreak of invasive infections due to resistant isolates of C. parapsilosis, we performed a 7-year retrospective and prospective analysis of 283 C. parapsilosis isolates collected in 240 patients, among whom 111 had invasive candidiasis. The study included a review of hospital records, genotyping analysis, and susceptibility testing that allowed us to determine the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall, the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcomes (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of C. parapsilosis to spread in an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.

International audience; The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of Candida parapsilosis isolates harbouring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understanding the epidemiology, pathogenicity and transmission of resistant Candida parapsilosis Faced with an outbreak of invasive infections due to resistant isolates of C. parapsilosis, we performed a 7-year retrospective and prospective analysis of 283 C. parapsilosis isolates collected in 240 patients, among who 111 had invasive candidiasis. Study included review of hospital records, genotyping analysis and susceptibility testing that allow determining the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcome (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of C. parapsilosis to spread on an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.

Objective Venoarterial extracorporeal membrane oxygenation (VA-ECMO) commonly is used to manage refractory cardiogenic shock after cardiac surgery, with 31% to 76% of patients successfully weaned off their ECMO. However, it is associated with high mortality rates, and 20% to 65% of weaned patients do not survive to hospital discharge. This study aimed to assess the incidence of ECMO weaning-related shock, the risk factors, and prognosis in the intensive care unit (ICU). Design Retrospective observational cohort study. Setting Surgical ICU of Cardiology Institute of Pitie-Salpetriere University Hospital (Paris-France). Participants Patients who were assisted with a peripheral VA-ECMO from January 2015 to December 2017 were included. Patients with venovenous, central, or right ECMO were excluded. Measurements The authors collected data on patients’ characteristics, during and after surgery. The indications for VA-ECMO implantation were ventricular dysfunction, primary graft dysfunction, and refractory cardiac arrest. Weaning-related shock was defined as the need to introduce or increase the dose of catecholamine at ECMO explantation or in the following week. Results After weaning off VA-ECMO, 56 of 146 patients (38.4%) presented weaning-related shock: 55% were septic shocks, 12.5 % were caused by right ventricle failure, and 7.1% by hemorrhage. ICU mortality was 42% versus 8% in patients who did not present shock. Multivariate analysis showed that patients with pulmonary hypertension and those with norepinephrine before weaning were more likely to develop shock. Conclusion ECMO weaning-related shock is frequent in patients with refractory cardiogenic shock after cardiac surgery. This is most commonly caused by sepsis and causes higher mortality rates, calling for further evaluation.

Background Cytomegalovirus (CMV) infection remains a common complication after heart transplantation (HTx). The association between CMV infection and allograft rejection is debated in the era of efficient prophylactic antiviral therapies. Methods This single-center cohort study utilized a highly phenotyped database of HTx recipients (2012-2016). The primary endpoint was the analysis of the association between CMV infection (CMV load ≥500 IU/mL whole blood) and the risk of allograft rejection (cellular rejection ≥1R1B, antibody-mediated rejection ≥pAMR1). Secondary endpoints included the analysis of a higher CMV load threshold (≥10,000 IU/mL) and different risk periods after PCR positivity. A mixed effect logistic regression model with a random intercept was applied. Results were adjusted for important risk factors of rejection. Results Overall, 384 patients were included and 6,388 CMV loads and 3,494 endomyocardial biopsies were analyzed. CMV infections ≥500 IU/mL were diagnosed on 1,223 (19.2%) blood samples from 284 (72.1%) patients and allograft rejections on 246 biopsies (7%) from 149 patients (38.8%). We did find not any association between CMV infection ≥500 IU/mL and rejection (univariable: OR 0.94, 95% CI [0.61, 1.45], p = 0.78, multivariable: OR 0.86, 95% CI [0.55, 1.33], p = 0.85). These results were consistent when analyzing a higher CMV load threshold and different periods of risk, reinforced by internal validation procedures and a posteriori calculation of the power (primary endpoint: power = 0.82, 95% CI [0.79-0.84]) and reproducible across different clinical scenarios. Conclusions CMV infection was not associated with an increased risk of rejection in a contemporary cohort of HTx recipients.

International audience

International audience; Objectives: Heart transplantation in patients supported by venoarterial extracorporeal membrane oxygenation has been associated with poor prognosis. A specific protocol for extracorporeal membrane oxygenation management encompassing patient selection, implantation strategy, and preoperative and perioperative treatment is applied at our institution. Our aim was to compare posttransplant outcomes of patients supported or not by extracorporeal membrane oxygenation at the time of heart transplantation.Design: A large observational single-center retrospective study was conducted. The primary endpoint was overall survival after heart transplantation. Secondary endpoints included death-censored rejection-free survival and the frequency of extracorporeal membrane oxygenation-related complications.Setting: One heart transplantation and extracorporeal membrane oxygenation high-volume center.Patients: All consecutive patients over 18 years old with a first noncombined heart transplantation performed between 2012 and 2016 were included.Interventions: None (retrospective observational study).Measurements and main results: Among the 415 transplanted patients, 118 (28.4%) were on extracorporeal membrane oxygenation at the time of transplantation (peripheral, 94%; intrathoracic, 6%). Median time on extracorporeal membrane oxygenation before heart transplantation was 9 days (interquartile range, 5-15 d) and median follow-up post heart transplantation was 20.7 months. Posttransplant survival did not differ significantly between the two groups (1-yr survival = 85.5% and 80.7% in extracorporeal membrane oxygenation vs nonextracorporeal membrane oxygenation patients; hazard ratio, 0.69; 95% CI, 0.43-1.11; p = 0.12, respectively). Donor age, body mass index, creatinine clearance, and ischemic time were independently associated with overall mortality, but not extracorporeal membrane oxygenation at the time of heart transplantation. Rejection-free survival also did not significantly differ between groups (hazard ratio, 0.85; 95% CI, 0.60-1.23; p = 0.39). Local wound infection was the most frequent complication after extracorporeal membrane oxygenation (37% of patients).Conclusions: With the implementation of a specific protocol, patients bridged to heart transplantation on extracorporeal membrane oxygenation had similar survival compared with those not supported by extracorporeal membrane oxygenation.

International audience

The use of nebulized antibiotics for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) increases worldwide. There is a paradox, however, between the large body of experimental evidence supporting the administration of nebulized rather than intravenous aminoglycosides and colistin to treat inoculation pneumonia caused by GNB [1, 2], and the paucity of clinical studies confirming such a benefit in VAP. Based on the recommendations of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [3, 4], the present article examines this apparent contradiction and suggests some directions for further research and clinical practice.

Purpose Cardiogenic shock due to post-resuscitation myocardial dysfunction is a major cause of mortality among patients hospitalized after cardiac arrest (CA). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been proposed in the most severe cases but the level of evidence is very low. We assessed characteristics, outcome and prognostic factors of patients treated with VA-ECMO for post-CA shock. Methods Using a large regional registry, we focused on all CA admitted in ICU. Among those who developed a post-CA shock, prognostic was compared according to VA-ECMO use, using logistic regression and propensity score. Specific prognostic factors were identified among VA-ECMO patients. Results Among 2988 patients admitted after CA, 1489 developed a post-CA shock, and were included. They were mostly male (68%), with mean age 63 years (SD=15). Fiflty-two patients (3.5%) were treated with VA-ECMO, mostly patients with ischemic cause of CA (67%). Among patients with post-CA shock, 312 (21%) were discharged alive (25% in VA-ECMO group, 21% in control group, P=0.45). After adjustment for pre-hospital and in-hospital factors, survival did not differ among patients treated with VA-ECMO (OR for survival=0.9, 95%CI 0.4–2.3, P=0.84). After propensity-score matching, results were consistent. Among patients treated with VA-ECMO, initial arterial pH (OR=1.7 per 0.1 increase, 95%CI 1.0–2.8, P=0.04) and implantation of VA-ECMO over 24h after ROSC (OR=20.0, 95%CI 1.4–277.3, P=0.03) were associated with survival. Conclusions Post-CA shock is frequent and is associated with a high mortality rate. When used in selected patients, we observed that VA-ECMO could be an appropriate treatment.