Publications by authors named "Bernard Cholley"

84 Publications

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia.

J Clin Med 2021 Oct 8;10(19). Epub 2021 Oct 8.

Université de Paris, F-75006 Paris, France.

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24-4.09; = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12-4.03; = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24-0.64; = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11-0.56; = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32-0.91; = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.
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http://dx.doi.org/10.3390/jcm10194618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509116PMC
October 2021

Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

PLoS One 2021 26;16(5):e0252026. Epub 2021 May 26.

INSERM UMRS 1138, Cordeliers Research Center, Team Inflammation, Complement, and Cancer, Paris, France.

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252026PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153504PMC
June 2021

Effectiveness of anaesthesia ventilator use for mechanical ventilation in critically ill patients during the COVID-19 pandemic.

Br J Anaesth 2021 07 12;127(1):e35-e37. Epub 2021 Apr 12.

Anaesthesiology and Critical Care Medicine Department, DMU PARABOL, Bichat Hospital, AP-HP, Paris, France; Université de Paris, FHU PROMICE, Paris, France; INSERM UMR 1152, ANR-10-LABX-17, Paris, France.

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http://dx.doi.org/10.1016/j.bja.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041185PMC
July 2021

A survey of patient blood management for patients undergoing cardiac surgery in nine European countries.

J Clin Anesth 2021 Sep 24;72:110311. Epub 2021 Apr 24.

Department of Anesthesiology; Erasmus Medical Center, Rotterdam, the Netherlands.

Study Objective: To describe and compare patient blood management (PBM) practices in cardiac surgery in nine European countries and identify the main risk factors for bleeding or transfusion according to the surveyed centres.

Design: We set up an online survey to evaluate PBM practices in two clinical scenarios, risk factors for bleeding or transfusion, and previous experience with antifibrinolytics.

Setting: This survey was completed by European anesthesiologists in 2019.

Patients: No patients were included in the survey.

Intervention: None.

Measurements: We evaluated the degree of implementation of PBM practices in patients undergoing cardiac surgery.

Main Results: Ninety-eight of 177 responses (38%) were complete with variable response rates by country. In a non-emergent situation, no respondents would transfuse red cells preoperatively in an anaemic patient, while cell salvage (89%) and antifibrinolytics (82%) would almost always be used. Optimization of Hemoglobin level (36%) and use of off-pump techniques (34%), minimally invasive surgery (25%) and relatively recently-developed CPB technologies such as mini-bypass (32%) and autologous priming (38%), varied greatly across countries. In an emergent clinical situation, topical haemostatic agents would frequently be used (61%). Tranexamic acid (72%) and aprotinin (20%) were the main antifibrinolytics used, with method of administration and dose varying markedly across countries. Five factors were considered to increase risk of bleeding or transfusion by at least 90% of respondents: pre-operative anaemia, prior cardiac surgery, clopidogrel 5 days or less before surgery, use of other P2Y12 inhibitors at any point, and thrombocytopenia <100.10 platelets/mm.

Conclusion: PBM guidelines are not universally implemented in European cardiac surgery centres or countries, resulting in discrepancies in techniques and products used for a given clinical situation.
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http://dx.doi.org/10.1016/j.jclinane.2021.110311DOI Listing
September 2021

Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study.

Lancet Respir Med 2021 08 19;9(8):851-862. Epub 2021 Apr 19.

Department of Cardiovascular and Thoracic Surgery, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France; Sorbonne University, INSERM UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.

Background: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic.

Methods: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO.

Findings: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm HO (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation.

Interpretation: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources.

Funding: None.
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http://dx.doi.org/10.1016/S2213-2600(21)00096-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055207PMC
August 2021

Perioperative hemodynamic optimization: from guidelines to implementation-an experts' opinion paper.

Ann Intensive Care 2021 Apr 14;11(1):58. Epub 2021 Apr 14.

Département d'Anesthésie-Réanimation, Hôpital Bichat Claude Bernard, AP-HP Nord, Paris, France.

Despite a large body of evidence, the implementation of guidelines on hemodynamic optimization and goal-directed therapy remains limited in daily routine practice. To facilitate/accelerate this implementation, a panel of experts in the field proposes an approach based on six relevant questions/answers that are frequently mentioned by clinicians, using a critical appraisal of the literature and a modified Delphi process. The mean arterial pressure is a major determinant of organ perfusion, so that the authors unanimously recommend not to tolerate absolute values below 65 mmHg during surgery to reduce the risk of postoperative organ dysfunction. Despite well-identified limitations, the authors unanimously propose the use of dynamic indices to rationalize fluid therapy in a large number of patients undergoing non-cardiac surgery, pending the implementation of a "validity criteria checklist" before applying volume expansion. The authors recommend with a good agreement mini- or non-invasive stroke volume/cardiac output monitoring in moderate to high-risk surgical patients to optimize fluid therapy on an individual basis and avoid volume overload. The authors propose to use fluids and vasoconstrictors in combination to achieve optimal blood flow and maintain perfusion pressure above the thresholds considered at risk. Although purchase of disposable sensors and stand-alone monitors will result in additional costs, the authors unanimously acknowledge that there are data strongly suggesting this may be counterbalanced by a sustained reduction in postoperative morbidity and hospital lengths of stay. Beside existing guidelines, knowledge and explicit clinical reasoning tools followed by decision algorithms are mandatory to implement individualized hemodynamic optimization strategies and reduce postoperative morbidity and duration of hospital stay in high-risk surgical patients.
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http://dx.doi.org/10.1186/s13613-021-00845-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046882PMC
April 2021

Major bleeding complications in critically ill patients with COVID-19 pneumonia.

J Thromb Thrombolysis 2021 Jul 1;52(1):18-21. Epub 2021 Mar 1.

Department of Anaesthesiology and Critical Care, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Université de Paris, Paris, France.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.
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http://dx.doi.org/10.1007/s11239-021-02403-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919235PMC
July 2021

Current use of inotropes in circulatory shock.

Ann Intensive Care 2021 Jan 29;11(1):21. Epub 2021 Jan 29.

Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, USA.

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.

Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions.

Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement).

Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.
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http://dx.doi.org/10.1186/s13613-021-00806-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846624PMC
January 2021

First human facial retransplantation: 30-month follow-up.

Lancet 2020 11;396(10264):1758-1765

Department of Plastic, Reconstructive, and Aesthetic Surgery, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris Descartes, Paris, France; Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Since the first successful facial transplantation in 2005, the benefits of this procedure in terms of aesthetics, functionality, and quality of life have been firmly established. However, despite immunosuppressive treatment, long-term survival of the allograft might be compromised by chronic antibody-mediated rejection (CAMR), leading to irreversible necrosis of the tissue. In the absence of therapeutic options, this complication is inevitably life-threatening.

Methods: We report facial retransplantation in a man, 8 years after his first facial transplantation because of extensive disfigurement from type 1 neurofibromatosis and 6 weeks after complete loss of his allograft due to severe CAMR. We describe the chronology of immune-related problems that culminated in allograft necrosis and the eventual loss of the facial transplant, the desensitisation protocol used for this highly immunosensitised recipient, the surgical technicalities of the procedure, the specific psychological management of this patient, and the results from follow-up at 30 months.

Findings: Although the patient had a complicated postoperative course with numerous immunological, infectious, cardiorespiratory, and psychological events, he was discharged after a hospital stay of almost 1 year. He has since been able to re-integrate into his community with acceptable restoration of his quality of life.

Interpretation: This clinical report of the first documented human facial retransplantation is proof-of-concept that the loss of a facial transplant after CAMR can be mitigated successfully by retransplantation combined with an aggressive desensitisation process.

Funding: Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris.
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http://dx.doi.org/10.1016/S0140-6736(20)32438-7DOI Listing
November 2020

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

Arterioscler Thromb Vasc Biol 2021 01 5;41(1):415-429. Epub 2020 Nov 5.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, France (N.G., A.B., E.R., S.I., S.L., A. Cras, N.N., J.R., P.G., D.M.S.).

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC) mesenchymal-like phenotype was confirmed by CD90/CD73/CD44 expression and multipotent-like differentiation ability. When VIC were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC-conditioned media and confirmed at the mRNA level in VIC compared with control VIC. Conditioned media from VIC induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC involvement in angiogenesis by a VEGF-A dependent mechanism.

Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
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http://dx.doi.org/10.1161/ATVBAHA.120.314287DOI Listing
January 2021

Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy.

PLoS One 2020 2;15(10):e0240241. Epub 2020 Oct 2.

Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Hemodynamic monitoring during digestive endoscopy is usually minimal and involves intermittent brachial pressure measurements. New continuous noninvasive devices to acquire instantaneous arterial blood pressure may be more sensitive to detect procedural hypotension.

Purpose: To compare the ability of noninvasive continuous monitoring with that of intermittent oscillometric measurements to detect hypotension during digestive endoscopy.

Methods: In this observational prospective study, patients scheduled for gastrointestinal endoscopy and colonoscopy under sedation were monitored using intermittent pressure measurements and a noninvasive continuous technique (ClearSight™, Edwards). Stroke volume was estimated from the arterial pressure waveform. Mean arterial pressure and stroke volume values were recorded at T1 (prior to anesthetic induction), T2 (after anesthetic induction), T3 (gastric insufflation), T4 (end of gastroscopy), T5 (colonic insufflation). Hypotension was defined as mean arterial pressure < 65 mmHg.

Results: Twenty patients (53±17 years) were included. Six patients (30%) had a hypotension detected using intermittent pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). Mean arterial pressure decreased during the procedure with respect to T1 (p < 0.05), but the continuous method provided an earlier warning than the intermittent method (T3 vs T4). Nine patients (45%) had at least a 25% reduction in stroke volume, with respect to baseline.

Conclusion: Noninvasive continuous monitoring was more sensitive than intermittent measurements to detect hypotension. Estimation of stroke volume revealed profound reductions in systemic flow. Noninvasive continuous monitoring in high-risk patients undergoing digestive endoscopy under sedation could help in detecting hypoperfusion earlier than the usual intermittent blood pressure measurements.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240241PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531858PMC
December 2020

Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy.

PLoS One 2020 2;15(10):e0240241. Epub 2020 Oct 2.

Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Hemodynamic monitoring during digestive endoscopy is usually minimal and involves intermittent brachial pressure measurements. New continuous noninvasive devices to acquire instantaneous arterial blood pressure may be more sensitive to detect procedural hypotension.

Purpose: To compare the ability of noninvasive continuous monitoring with that of intermittent oscillometric measurements to detect hypotension during digestive endoscopy.

Methods: In this observational prospective study, patients scheduled for gastrointestinal endoscopy and colonoscopy under sedation were monitored using intermittent pressure measurements and a noninvasive continuous technique (ClearSight™, Edwards). Stroke volume was estimated from the arterial pressure waveform. Mean arterial pressure and stroke volume values were recorded at T1 (prior to anesthetic induction), T2 (after anesthetic induction), T3 (gastric insufflation), T4 (end of gastroscopy), T5 (colonic insufflation). Hypotension was defined as mean arterial pressure < 65 mmHg.

Results: Twenty patients (53±17 years) were included. Six patients (30%) had a hypotension detected using intermittent pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). Mean arterial pressure decreased during the procedure with respect to T1 (p < 0.05), but the continuous method provided an earlier warning than the intermittent method (T3 vs T4). Nine patients (45%) had at least a 25% reduction in stroke volume, with respect to baseline.

Conclusion: Noninvasive continuous monitoring was more sensitive than intermittent measurements to detect hypotension. Estimation of stroke volume revealed profound reductions in systemic flow. Noninvasive continuous monitoring in high-risk patients undergoing digestive endoscopy under sedation could help in detecting hypoperfusion earlier than the usual intermittent blood pressure measurements.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240241PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531858PMC
December 2020

Percutaneous cannulation for extracorporeal membrane oxygenation (ECMO): A method for pig experimental models.

MethodsX 2020 29;7:100979. Epub 2020 Jun 29.

Department of Anesthesiology and Pain Medicine, UC Davis School of Medicine, Sacramento, USA.

Pigs are often used for experimental models of cardiogenic shock, cardiac arrest or acute lung injury with veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO) implementation. Percutaneous (as opposed to surgical) cannulation in experimental models has potential advantages, including, less surgical trauma or stressful stimuli and less bleeding complications when compared to open chest cannulation. However, pig anatomy can also be a challenge because of the deep location and angled anatomy of the femoral artery. The Seldinger technique and the use of a percutaneous cannulation kit is feasible in pigs. Summarized here we present (Graphical Abstract):•Percutaneous ECMO cannulation method for non-cardiac surgeon.•Establishment of this simple and rapid methods for pig experimental models.•Predictable complications of this method.
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http://dx.doi.org/10.1016/j.mex.2020.100979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338622PMC
June 2020

Recommendations for core critical care ultrasound competencies as a part of specialist training in multidisciplinary intensive care: a framework proposed by the European Society of Intensive Care Medicine (ESICM).

Crit Care 2020 07 3;24(1):393. Epub 2020 Jul 3.

European Society of Intensive Care Medicine, Brussels, Belgium.

Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed.

Background/aim: Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care.

Methods: A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory.

Results: The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid.

Conclusion: The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described.
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http://dx.doi.org/10.1186/s13054-020-03099-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333303PMC
July 2020

Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients.

Am J Respir Crit Care Med 2020 09;202(6):822-829

Paris University, Paris, France.

Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function. In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid. A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m at ICU admission. In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8];  = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8];  < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1). Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.
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http://dx.doi.org/10.1164/rccm.201910-1950OCDOI Listing
September 2020

Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study.

Can J Anaesth 2020 09 4;67(9):1162-1169. Epub 2020 Jun 4.

Department of Anaesthesia and Critical Care Medicine, Georges-Pompidou European Hospital, APHP, 20, rue Leblanc, 75015, Paris, France.

Purpose: The pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness.

Methods: Secondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250-500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve.

Results: The three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P < 0.01, P = 0.03, and P < 0.01, respectively). The median [interquartile range] predictive score, calculated after discretization of these parameters according to their optimal threshold value was 3 [2-3] in fluid responders and 1 [1-2] in fluid non-responders, respectively (P < 0.001). The area under the curve of the predictive score was 0.807 (95% confidence interval, 0.662 to 0.909; P < 0.001).

Conclusion: A multiparametric score combining three parameters generated by the PRAM monitor can predict fluid responsiveness with good positive and negative predictive values in intensive care unit patients.
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http://dx.doi.org/10.1007/s12630-020-01736-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271959PMC
September 2020

Haemodynamic management during hyperthermic intraperitoneal chemotherapy: A systematic review.

Anaesth Crit Care Pain Med 2020 08 19;39(4):531-542. Epub 2020 Apr 19.

Service d'anesthésie, hôpitaux universitaires Paris Ouest, hôpital européen Georges Pompidou, Assistance publique-Hôpitaux de Paris, 20, rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Context: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a surgical technique for peritoneal carcinomatosis combining cytoreduction surgery and peritoneal irrigation of cytotoxic agents responsible for haemodynamics and fluid homeostasis alterations. To this day, no guidelines exist concerning intraoperative management.

Objectives: To review data on haemodynamic monitoring and management of patients undergoing HIPEC and to help design a standardised anaesthetic protocol.

Data Sources: MEDLINE, EMBASE and Cochrane library were searched using the following.

Study Selection: Original articles and case-reports. Letters to editors and reviews were excluded.

Data Extraction: Data on haemodynamic management, morbidity and mortality.

Data Synthesis: Haemodynamic management during HIPEC is highly variable and depends on local protocols. Only one randomised controlled trial evaluated the benefit of goal-directed fluid administration (GDFA). GDFA guided by advanced haemodynamic monitoring resulted in significantly less complication, shorter length of stay and less mortality compared to standard fluid administration. Renal protection protocol did not decrease the risk of acute kidney injury (AKI).

Conclusion: Our review reveals that fluid administration guided by advanced monitoring seems to be associated with less postoperative morbidity and mortality after HIPEC. Nevertheless, the literature review shows that intraoperative haemodynamic management is highly variable for this surgery. The use of renal protection strategy does not decrease the prevalence of AKI. Further prospective trials comparing different fluid management and haemodynamic monitoring strategies are urgently needed (PROSPERO registration CRD42018115720).
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http://dx.doi.org/10.1016/j.accpm.2020.03.019DOI Listing
August 2020

Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study.

Anesthesiology 2020 02;132(2):267-279

From the Department of Biostatistics, Bichat-Claude Bernard Hospital, AP-HP.Nord, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France (C.C., F.M.) University of Paris, IAME, UMR1137, Paris, France (C.C., X.D., F.M.) INSERM, IAME, UMR 1137, Paris, France (C.C., X.D., F.M.) Clinical Investigation Center, CIC-1425, AP-HP, INSERM, Paris, France (X.D., Y.C.D.B.) Department of Anesthesiology and Critical Care Medicine, Hôpital Pitié-Salpêtrière, APHP, Sorbonne University, UPMC University, Paris 06, UMR INSERM 1166, IHU ICAN, Paris, France (J.A., N.A.-H.) Department of Anesthesia and Intensive Care, Hôpital Européen Georges Pompidou, APHP Paris-Ouest, University of Paris, Paris, France (B.C.) Department of Anesthesia and Intensive Care, Hôpital Cardiologique Louis Pradel, IHU OPERA Inserm U1060/Faculté de Médecine Lyon Est, University Claude Bernard Lyon 1, Lyon, France (J.-L.F.) Department of Cardiac Surgery, Bichat-Claude Bernard Hospital, AP-HP.Nord, APHP, Paris, France (P.N.) Department of Anesthesia and Intensive Care, Bichat-Claude Bernard Hospital, AP-HP.Nord, APHP, Paris, France (M.-P.D., S.P., P.M., D.L.) University of Paris, Paris, France (P.M., D.L.).

Background: For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation.

Methods: This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of β-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of β-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed).

Results: Of 663 patients, β-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of β-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h.

Conclusions: β-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) β-blocker reintroduction after cardiac surgery.
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http://dx.doi.org/10.1097/ALN.0000000000003064DOI Listing
February 2020

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper.

Crit Care 2019 Nov 29;23(1):385. Epub 2019 Nov 29.

Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.
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http://dx.doi.org/10.1186/s13054-019-2674-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883606PMC
November 2019

Reply to the comments of Dr Fayssoil.

J Clin Monit Comput 2020 06 20;34(3):617. Epub 2019 Nov 20.

Hôpital Européen Georges Pompidou, AP-HP, Paris, France.

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http://dx.doi.org/10.1007/s10877-019-00427-4DOI Listing
June 2020

Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial.

Intensive Care Med 2019 10 1;45(10):1401-1412. Epub 2019 Oct 1.

Département d'Anesthésie et Réanimation (SAR 2), CHU La Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.

Purpose: To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery.

Methods: In a pragmatic, randomized, multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm HO) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm HO). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days.

Results: Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (p = 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%; p = 0.77), non-invasive ventilation (13.2% vs 15.5%; p = 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%, p = 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day, p = 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups.

Conclusions: A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery.

Trial Registration: Clinicaltrials.gov Identifier: NCT02866578. https://clinicaltrials.gov/ct2/show/NCT02866578.
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http://dx.doi.org/10.1007/s00134-019-05741-8DOI Listing
October 2019

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

Crit Care Med 2019 12;47(12):e953-e961

Department of Anaesthesiology, Critical Care Medicine and Burn unit, AP-HP, Saint Louis and Lariboisière University Hospitals, Paris, France.

Objectives: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge.

Design: Ancillary investigation of a prospective observational study.

Setting: Twenty-one ICUs with 1-year follow-up.

Patients: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included.

Interventions: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors.

Measurements And Main Results: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease).

Conclusions: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.
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http://dx.doi.org/10.1097/CCM.0000000000004010DOI Listing
December 2019

Association of Early, High Plasma-to-Red Blood Cell Transfusion Ratio With Mortality in Adults With Severe Bleeding After Trauma.

JAMA Netw Open 2019 09 4;2(9):e1912076. Epub 2019 Sep 4.

Service d'Anesthésie-réanimation, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.

Importance: Optimal transfusion management is crucial when treating patients with trauma. However, the association of an early, high transfusion ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBC) with survival remains uncertain.

Objective: To study the association of an early, high FFP-to-PRBC ratio with all-cause 30-day mortality in patients with severe bleeding after trauma.

Design, Setting, And Participants: This cohort study analyzes the data included in a multicenter national French trauma registry, Traumabase, from January 2012 to July 2017. Traumabase is a prospective, active, multicenter adult trauma registry that includes all consecutive patients with trauma treated at 15 trauma centers in France. Overall, 897 patients with severe bleeding after trauma were identified using the following criteria: (1) received 4 or more units of PRBC during the first 6 hours or (2) died from hemorrhagic shock before receiving 4 units of PRBC.

Exposures: Eligible patients were divided into a high-ratio group, defined as an FFP-to-PRBC ratio more than 1:1.5, and a low-ratio group, defined as an FFP-to-PRBC ratio of 1:1.5 or less. The ratio was calculated using the cumulative units of FFP and PRBC received during the first 6 hours of management.

Main Outcomes And Measures: A Cox regression model was used to analyze 30-day survival with the transfusion ratio as a time-dependent variable to account for survivorship bias.

Results: Of the 12 217 patients included in the registry, 897 (7.3%) were analyzed (median [interquartile range] age, 38 (29-54) years; 639 [71.2%] men). The median (interquartile range) injury severity score was 34 (22-48), and the overall 30-day mortality rate was 33.6% (301 patients). A total of 506 patients (56.4%) underwent transfusion with a high ratio and 391 (43.6%) with a low ratio. A high transfusion ratio was associated with a significant reduction in 30-day mortality (hazard ratio, 0.74; 95% CI, 0.58-0.94; P = .01). When only analyzing patients who had complete data, a high transfusion ratio continued to be associated with a reduction in 30-day mortality (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04).

Conclusions And Relevance: In this analysis of the Traumabase registry, an early FFP-to-PRBC ratio of more than 1:1.5 was associated with increased 30-day survival among patients with severe bleeding after trauma. This result supports the use of early, high FFP-to-PRBC transfusion ratios in patients with severe trauma.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.12076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763975PMC
September 2019

An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis.

Sci Transl Med 2019 07;11(500)

Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM, 75015 Paris, France.

Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.
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http://dx.doi.org/10.1126/scitranslmed.aat1479DOI Listing
July 2019

Early changes in diaphragmatic function evaluated using ultrasound in cardiac surgery patients: a cohort study.

J Clin Monit Comput 2020 Jun 5;34(3):559-566. Epub 2019 Jul 5.

Department of Anesthesia and Intensive Care, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.

Little is known about the evolution of diaphragmatic function in the early post-cardiac surgery period. The main purpose of this work is to describe its evolution using ultrasound measurements of muscular excursion and thickening fraction (TF). Single-center prospective study of 79 consecutive uncomplicated elective cardiac surgery patients, using motion-mode during quiet unassisted breathing. Excursion and TF were measured sequentially for each patient [pre-operative (D1), 1 day (D2) and 5 days (D3) after surgery]. Pre-operative median for right and left hemidiaphragmatic excursions were 1.8 (IQR 1.6 to 2.1) cm and 1.7 (1.4 to 2.0) cm, respectively. Pre-operative median right and left thickening fractions were 28 (19 to 36) % and 33 (22 to 51) %, respectively. At D2, there was a reduction in both excursion (right: 1.5 (1.1 to 1.8) cm, p < 0.001, left: 1.5 (1.1 to 1.8), p = 0.003) and thickening fractions (right: 20 (15 to 34) %, p = 0.021, left: 24 (17 to 39) %, p = 0.002), followed by a return to pre-operative values at D3. A positive moderate correlation was found between excursion and thickening fraction (Spearman's rho 0.518 for right and 0.548 for left hemidiaphragm, p < 0.001). Interobserver reliability yielded a bias below 0.1 cm with limits of agreement (LOA) of ± 0.3 cm for excursion and - 2% with LOA of ± 21% for thickening fractions. After cardiac surgery, the evolution of diaphragmatic function is characterized by a transient impairment followed by a quick recovery. Although ultrasound diaphragmatic excursion and thickening fraction are correlated, excursion seems to be a more feasible and reproducible method in this population.
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http://dx.doi.org/10.1007/s10877-019-00350-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223646PMC
June 2020

Spironolactone and perioperative atrial fibrillation occurrence in cardiac surgery patients: Rationale and design of the ALDOCURE trial.

Am Heart J 2019 08 9;214:88-96. Epub 2019 May 9.

Université Caen Normandie, Medical School, UNICAEN, CHU Caen, EA, 4650, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen F-14000, France; Department of Cardiology, CHU de Caen, Caen, F-14000, France.

Background: After artery bypass grafting (CABG), the presence of perioperative AF (POAF) is associated with greater short- and long-term cardiovascular morbidity. Underlying POAF mechanisms are complex and include the presence of an arrhythmogenic substrate, cardiac fibrosis and electrical remodeling. Aldosterone is a key component in this process. We hypothesize that perioperative mineralocorticoid receptor (MR) blockade may decrease the POAF incidence in patients with a left ventricular ejection fraction (LVEF) ≥50% who are referred for CABG with or without aortic valve replacement (AVR).

Study Design: The ALDOCURE trial (NCT03551548) will be a multicenter, randomized, double-blind, placebo-controlled trial testing the superiority of a low-cost MR antagonist (MRA, spironolactone) on POAF in 1500 adults referred for on-pump elective CABG surgery with or without AVR, without any history of heart failure or atrial arrhythmia. The primary efficacy end point is the occurrence of POAF from randomization to within 5 days after surgery, assessed in a standardized manner. The main secondary efficacy end points include the following: postoperative AF occurring within 5 days after cardiac surgery, perioperative myocardial injury, major cardiovascular events and death occurring within 30 days of surgery, hospital and intensive care unit length of stay, need for readmission, LVEF at discharge and significant ventricular arrhythmias within 5 days after surgery. Safety end points, including blood pressure, serum potassium levels and renal function, will be monitored regularly throughout the trial duration.

Conclusion: The ALDOCURE trial will assess the effectiveness of spironolactone in addition to standard therapy for reducing POAF in patients undergoing CABG.

Clinical Trial Registration: NCT03551548.
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http://dx.doi.org/10.1016/j.ahj.2019.04.023DOI Listing
August 2019

Should we keep levosimendan in our pharmacies? Yes, undoubtedly!

Anaesth Crit Care Pain Med 2019 06;38(3):211-212

Service d'anesthésie-réanimation, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.

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http://dx.doi.org/10.1016/j.accpm.2019.04.007DOI Listing
June 2019
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