Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The INHALE trial: multiple reasons for a negative result.

The INHALE trial, a Bayer-sponsored phase 3 trial in critically ill patients with pneumonia caused by Gram-negative bacteria by Michael Niederman and colleagues,1 did not find aerosolised amikacin as an adjunctive therapy to intravenous antibiotics to be superior to intravenous antibiotics alone. The study design, the doses of amikacin, and the technique of nebulisation are all likely to explain this negative result. [...

Weaning-Related Shock in Patients With ECMO: Incidence, Mortality, and Predisposing Factors

International audienceObjective: 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 Pitié-Salpêtrière 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

Beneficial role of adipose‐derived mesenchymal stem cells from microfragmented fat in a murine model of duchenne muscular dystrophy

International audienceIntroduction: No etiologic therapy is available for Duchenne muscular dystrophy (DMD), but mesenchymal stem cells were shown to be effective in preclinical models of DMD. The objective of this study is to investigate the effect of microfragmented fat extracted on a murine model of DMD.Methods: Fat tissue was extracted from healthy human participants and injected IM into DMD mice. Histological analysis, cytokines, and force measurement were performed up to 4 weeks after injection.Results: Duchenne muscular dystrophy mice injected with microfragmented fat exhibited an improved muscle phenotype (decreased necrosis and fibrosis), a decrease of inflammatory cytokines, and increased strength.Discussion: Administration of microfragmented fat in key muscles may improve muscular phenotype in patients with DMD

Practice Patterns of Antithrombotic Therapy during the Early Postoperative Course of Cardiac Surgery

International audienceBackground: 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

Postoperative serum levels of Endocan are associated with the duration of norepinephrine support after coronary artery bypass surgery

International audienceBACKGROUND : Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response and an endothelial dysfunction, whose qualitative assessment appears to be a major issue. Endocan (ESM-1, endothelial cell specific molecule-1) is a protein preferentially expressed by the endothelium and previously associated with prognosis of septic shock or acute respiratory distress syndrome. In this pilot study, we investigated the kinetic of Endocan in planned coronary artery bypass grafting (CABG) surgery with CPB.PATIENTS AND METHODS : We conducted an observational, prospective, mono centre study. All adult patients with left systolic ejection fraction>50%, undergoing planned on-pump CABG, were screened for inclusion. A written informed consent was obtained. Measurements and main results Serum Endocan concentrations were respectively 2.4 [2.1-3.0] ng. mL-1, 10.4 [7.4-13.9] ng.mL-1, 5.7 [4.4-8.2] ng.mL-1, and 5.4 [4.1-7.5] ng.mL-1 at day 0, day 1, day 3 and day 5. Endocan concentrations increased at day 1, day 3, and day 5 in comparison with preoperative concentration (P<0.001). In the multivariate analysis, age (P=0.002), history of acute coronary syndrome (P=0.024) and the catecholamine-free days at day 28 (P=0.007) were associated to the increase of perioperative Endocan concentrations.CONCLUSION : Serum Endocan concentration increases after CABG surgery with CPB until day 1. The norepinephrine support increases the risk of Endocan release, suggesting a relationship between the kinetic of Endocan and the vasoplegic syndrome. At day 3, Endocan concentration decreases slowly but is not normalised at day 5. Further studies should investigate the prognostic value of the magnitude of postoperative Endocan concentration after cardiac surgery

Hospital outbreak of fluconazole-resistant Candida parapsilosis: arguments for clonal transmission and long-term persistence

International audienceThe 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

Prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis of non-pharmacological interventions

Abstract Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI. Methods We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence. Results We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40–0.76], I 2 = 0%; P het = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78–0.95]; I 2 = 23%; P het = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I 2 = 53%; P het < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; P het = 0.67; I 2 = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; P het = 0.25; I 2 = 26%). Conclusions Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning