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Background Mechanical ventilation (MV) is the cornerstone in the management of the acute respiratory distress syndrome (ARDS). Recent research suggests that decreasing the intensity of MV using lung protective ventilation (LPV) with lower tidal volume (Vt) and driving pressure (∆P) could improve survival. Extra-corporal CO2 removal (ECCO2R) precisely enables LPV by allowing lower Vt, ∆P and mechanical power while maintaining PaCO2 within a physiologic range. This study evaluates the potential cost-effectiveness of ECCO2R-enabled LPV in France. Methods We modelled the distribution over time of ventilated ARDS patients across 3 health-states (alive & ventilated, alive & weaned from ventilation, dead). We compared the outcomes of 3 strategies: MV (no ECCO2R), LPV (ECCO2R when PaCO2 > 55 mmHg) and Ultra-LPV (ECCO2R for all). Patients characteristics, ventilation settings, survival and lengths of stay were derived from a large ARDS epidemiology study. Survival benefits associated with lower ∆P were taken from the analysis of more than 3000 patients enrolled in 9 randomized trials. Health outcomes were expressed in quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were computed with both Day 60 cost and Lifetime cost. Results Both LPV and ULPV as enabled by ECCO2R provided favorable results at Day 60 as compared to MV. Survival rates were increased with the protective strategies, notably with ULPV that provided even more manifest benefits as compared to MV. LPV and ULPV produced +0.162 and + 0.627 incremental QALYs as compared to MV, respectively. LPV and ULPV costs were augmented because of their survival benefits. Nonetheless, ICERs of LPV and ULPV vs. MV were all well below the €50,000 threshold. ULPV also presented with favorable ICERs as compared to LPV (i.e. less than €25,000/QALY). Conclusions ECCO2R-enabled LPV strategies might provide cost-effective survival benefit. Additional data from interventional and observational studies are needed to support this preliminary model-based analysis.

Background Critical illness-related corticosteroid insufficiency (CIRCI) is common during critical illness and is usually associated with poor outcomes, as prolonged duration of mechanical ventilation (MV) and higher mortality. CIRCI may alter cardiac and vascular functions. Weaning-induced pulmonary oedema (WiPO) is a major mechanism of weaning failure. The aim of this study was to evaluate the role of CIRCI in patients with difficult ventilator weaning and its possible relation with WiPO. Methods This is a prospective study conducted in the intensive care of a university hospital in France. Patients under MV for more than 24 h, meeting weaning criteria and having failed the first spontaneous breathing trial (SBT) underwent a corticotropin stimulation test, with assessment of total blood cortisol levels immediately before (T0) 0.25 mg iv of tetracosactrin and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0. CIRCI was defined as T0 max max Results Seventy-six consecutive patients (63 ± 14 years; 49 men) with difficult weaning were enrolled. CIRCI and inadequate adrenal reserve occurred in 25 (33%) and 17 (22%) patients, respectively. The probability of successful extubation was significantly decreased in patients with CIRCI or inadequate adrenal reserve, as compared to their counterparts, and this association persisted after adjustment on severity (SOFA score at first SBT). WiPO occurred in 44 (58%) and 8 (11%) patients, according to the liberal and conservative definition, respectively. WiPO was not associated with CIRCI nor with inadequate adrenal reserve. Conclusion CIRCI was common during difficult weaning and was associated with its prolongation. We did not find a significant association between CIRCI and WiPO.

Background The approach for veno-arterial extracorporeal membrane oxygenation implantation (VA-ECMO) in patients with cardiogenic shock can be either surgical or percutaneous. Complete angio-guided percutaneous implantation and explantation could decrease vascular complications. We sought to describe the initial results of complete percutaneous angio-guided ECMO implantation and explantation using preclosing. Methods All consecutive patients who underwent peripheral femoro-femoral VA-ECMO percutaneous implantation for refractory cardiogenic shock or cardiac arrest were enrolled in a prospective registry (03/2018–12/2020). Percutaneous preclosing using two closing devices (Perclose ProGlide, Abbott) inserted before cannulation was used in both femoral artery and vein. Explantation was performed using a crossover technique under angiographic guidance. The occurrence of vascular complication was recorded. Results Among the 56 patients who underwent percutaneous VA-ECMO implantation for cardiogenic shock or refractory cardiac arrest, 41 underwent preclosing. Femoral vessel cannulation was successful in all patients and total cannulation time was 20 (10–40) min. Weaning from ECMO was possible in 22/41 patients (54%) and 12 (29%) patients were alive at day 30. Significant vascular complications occurred in 2/41 patients. Percutaneous decannulation was performed in 20 patients with 19/20 technical success rate. All femoral arteries and veins were properly closed using the pre-closing devices without bleeding on the angiographic control except for one patient in whom surgical closure of the artery was required. No patient required transfusion for access related significant bleeding and no other vascular complication occurred. Furthermore, no groin infection was observed after full percutaneous implantation and removal of ECMO. Conclusion Emergent complete percutaneous angio-guided VA-ECMO implantation and explantation using pre-closing technique can be an attractive strategy in patients referred for refractory cardiogenic shock.

Auteurs : The HOPEFUL Study group; International audience; No abstract available

Purpose To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. Methods Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. Results Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. Conclusions PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-00994-9.

Purpose Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. Methods Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. Results 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. Conclusions The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates. Electronic supplementary material The online version of this article (10.1007/s00134-020-06323-9) contains supplementary material, which is available to authorized users.

Background Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis. Methods Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference. Results Sixty-seven patients were assessed (55 males), with a median age of 61 [50–70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers’ concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices. Conclusions In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. β-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a β-blocker (atenolol) during murine peritonitis. Methods Ivabradine (3 μg/g), atenolol (3 μg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile). Results As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224). Conclusions Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

Background There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. Methods This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. Results From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). Conclusions An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.

Background Compared to other life-threatening infection survivors, long-term health-related quality of life (QOL) of patients surviving necrotizing soft-tissue infections (NSTI) and its determinants are little known. In this monocentric prospective cohort including NSTI survivors admitted between 2014 and 2017, QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36), the Hospital Anxiety and Depression (HAD), the activity of daily living (ADL), instrumental ADL (IADL) scales and the Impact of Event Scale-Revised (IES-R). The primary outcome measure was the SF-36 physical component summary (PCS). NSTI patients were compared according to intensive care unit (ICU) admission status. ICU survivors were matched on SAPS II with non-NSTI related septic shock survivors. Results Forty-nine NSTI survivors were phone-interviewed and included in the study. Median PCS was decreased compared to the reference population [− 0.97 (− 2.27; − 0.08) SD]. Previous cardiac disease was the only variable associated with PCS alteration [multivariate regression coefficient: − 8.86 (− 17.64; − 0.07), p = 0.048]. Of NSTI survivors, 15.2% had a HAD-D score ≥ 5 and 61.2% an IES-R score ≥ 33. ICU admission was not associated with lower PCS [35.21 (25.49–46.54) versus (vs) 41.82 (24.12–51.01), p = 0.516], but with higher IES-R score [14 (7.5–34) vs 7 (3–18), p = 0.035] and a higher proportion of HAD-D score ≥ 5 (28.6 vs 4.0%, p = 0.036). Compared to non-NSTI septic shock-matched controls, NSTI patients had similar PCS [33.81 (24.58; − 44.39) vs 44.87 (26.71; − 56.01), p = 0.706] but higher HAD-D [3.5 (1–7) vs 3 (1.5–6), p = 0.048] and IES-R scores [18 (8–35) vs 8 (3–19), p = 0.049]. Conclusions Long-term QOL in NSTI survivors is severely impaired, similarly to that of non-NSTI septic shock patients for physical compartments, but with more frequent depressive and/or post-traumatic stress disorders. Only ICU admission and previous cardiac disease were predictive of QOL impairment.

Clinical manifestations of coronavirus disease 2019 in pregnant women, in contrast to previous outbreaks, seem to be similar to those of nonpregnant women. During severe acute respiratory syndrome (SARS), SARS influenza A, and Middle East respiratory syndrome outbreaks, an increased severity of disease among pregnant women was observed. In some pregnant women, respiratory failure can occur and progress quickly to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) as a rescue therapy. Despite a lack of current guidelines on the use of ECMO in pregnant or postpartum women, this support therapy is an effective salvage therapy for patients with cardiac and/or respiratory failure, and is associated with favorable maternal and fetal outcomes. Herein, the authors report a case of severe COVID-19 disease in a pregnant patient after urgent cesarean delivery, who was treated successfully with ECMO during the postpartum. Extracorporeal membrane oxygenation should be considered early when conventional therapy is ineffective, and it is essential to refer to ECMO expert centers.

Patients with severe lung injury usually have a high respiratory drive, resulting in intense inspiratory effort that may even worsen lung damage by several mechanisms gathered under the name “patient-self inflicted lung injury” (P-SILI). Even though no clinical study has yet demonstrated that a ventilatory strategy to limit the risk of P-SILI can improve the outcome, the concept of P-SILI relies on sound physiological reasoning, an accumulation of clinical observations and some consistent experimental data. In this review, we detail the main pathophysiological mechanisms by which the patient’s respiratory effort could become deleterious: excessive transpulmonary pressure resulting in over-distension; inhomogeneous distribution of transpulmonary pressure variations across the lung leading to cyclic opening/closing of nondependent regions and pendelluft phenomenon; increase in the transvascular pressure favoring the aggravation of pulmonary edema. We also describe potentially harmful patient-ventilator interactions. Finally, we discuss in a practical way how to detect in the clinical setting situations at risk for P-SILI and to what extent this recognition can help personalize the treatment strategy.

Background The mechanisms of organ failure during sepsis are not fully understood. The hypothesis of circulating factors has been suggested to explain septic myocardial dysfunction. We explored the biological coherence of a large panel of sepsis mediators and their clinical relevance in septic myocardial dysfunction and organ failures during human septic shock. Methods Plasma concentrations of 24 mediators were assessed on the first day of septic shock using a multi-analyte cytokine kit. Septic myocardial dysfunction and organ failures were assessed using left ventricle ejection fraction (LVEF) and the Sequential Organ Failure Assessment score, respectively. Results Seventy-four patients with septic shock (and without immunosuppression or chronic heart failure) were prospectively included. Twenty-four patients (32%) had septic myocardial dysfunction (as defined by LVEF

Background Diaphragmatic dysfunction may promote weaning difficulties in patients who are mechanically ventilated. Objective The goal of this study was to assess whether diaphragm dysfunction detected by ultrasound prior to extubation could predict extubation failure in the ICU. Methods This multicenter prospective study included patients at high risk of reintubation: those aged > 65 years, with underlying cardiac or respiratory disease, or intubated > 7 days. All patients had successfully undergone a spontaneous breathing trial. Diaphragmatic function was assessed by ultrasound prior to extubation while breathing spontaneously on a T-piece. Bilateral diaphragmatic excursion and apposition thickening fraction were measured, and diaphragmatic dysfunction was defined as excursion Results Over a 20-month period, 191 at-risk patients were studied. Among them, 33 (17%) were considered extubation failures. The proportion of patients with diaphragmatic dysfunction was similar between those whose extubation succeeded and those whose extubation failed: 46% vs 51% using excursion (P = .55), and 71% vs 68% using thickening (P = .73), respectively. Values of excursion and thickening did not differ between the success and the failure groups: at right, excursion was 14 ± 7 mm vs 11 ± 8 (P = .13), and thickening was 29 ± 29% vs 38 ± 48% (P = .83), respectively. Extubation failure rates were 7%, 22%, and 46% in patients with effective, moderate, and ineffective cough (P Conclusions Diaphragmatic dysfunction assessed by ultrasound was not associated with an increased risk of extubation failure.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Neutrophil extracellular traps have been associated with tissue damage. Whether these are involved in the pathogenesis of human acute respiratory distress syndrome (ARDS) and could be a potential therapeutic target is unknown. The authors quantified bronchoalveolar and blood neutrophil extracellular traps in patients with pneumonia-related ARDS and assessed their relationship with ventilator-free days. Methods Immunocompetent patients with pneumonia and moderate or severe ARDS (n = 35) and controls (n = 4) were included in a prospective monocentric study. Neutrophil extracellular trap concentrations were quantified (as DNA–myeloperoxidase complexes) in bronchoalveolar lavage fluid and serum by enzyme-linked immunosorbent assay. The relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and the primary clinical endpoint (i.e., the number of live ventilator-free days at day 28) was assessed using linear regression analyses. Results There was no significant relationship between bronchoalveolar lavage neutrophil extracellular trap concentrations and ventilator-free days by multiple regression analysis (β coefficient = 2.40; 95% CI, −2.13 to 6.92; P = 0.288). Neutrophil extracellular trap concentrations were significantly higher in bronchoalveolar lavage than in blood of ARDS patients (median [first to third quartiles]:154 [74 to 1,000] vs. 26 [4 to 68] arbitrary units, difference: −94; 95% CI, −341 to −57; P < 0.0001). Bronchoalveolar concentrations of patients were higher than those of controls (154 [74 to 1,000] vs. 4 [4 to 4] arbitrary units, difference: −150; 95% CI, −996 to −64; P < 0.001) and associated with bronchoalveolar interleukin-8 (Spearman’s ρ = 0.42; P = 0.012) and neutrophil concentrations (ρ = 0.57; P < 0.0001). Intensive care unit mortality (12%, n = 2 of 17 vs. 17%, n = 3 of 18; P > 0.99) and the number of ventilator-free days at day 28 (22 [14 to 25] vs. 14 [0 to 21] days; difference: −5; 95% CI, −15 to 0; P = 0.066) did not significantly differ between patients with higher (n = 17) versus lower (n = 18) bronchoalveolar neutrophil extracellular trap concentrations. Conclusions Bronchoalveolar neutrophil extracellular trap concentration was not significantly associated with mechanical ventilation duration in pneumonia-related ARDS.

Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper “Th1-Th17” profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19., Author summary This study was the first to use shotgun metagenomics and in-depth bioanalysis of metagenomics data to understand the role of viral genomics, microorganism metagenomics and host transcriptomics in the severity of COVID-19. The study was performed using nasopharyngeal swabs collected from 104 patients with various severities of COVID-19 at the time of diagnosis. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. In contrast, host transcriptomic analyses showed that severe COVID-19 pneumonia is associated with overexpression of cytokine transcripts that activate the CXCR2 receptor pathway, whereas patients with benign disease present with a T helper “Th1-Th17” profile. The latter profile was associated with female gender and a lower mortality rate. These findings indicate that the most severe cases of COVID-19 are caused by excess neutrophil infiltration that enhances the inflammatory response and prolongs tissue damage. They suggest that CXCR2 antagonists, in particular IL-8 antagonists, could be promising candidates for the treatment of patients with severe COVID-19.

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. Conclusions IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

Background Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. Methods This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. Results In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. Conclusions In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.

Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015–2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%–19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95–0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05–1.14; p p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97–0.98; p p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.

Rationale Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS). Objectives To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse. Methods Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic. Results As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p 2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance. Conclusion An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.

BackgroundMicroaspiration of gastric and oropharyngeal secretions is the main causative mechanism of ventilator-associated pneumonia (VAP). Transesophageal echocardiography (TEE) is a routine investigation tool in intensive care unit and could enhance microaspiration. This study aimed at evaluating the impact of TEE on microaspiration and VAP in intubated critically ill adult patients.MethodsIt is a four-center prospective observational study. Microaspiration biomarkers (pepsin and salivary amylase) concentrations were quantitatively measured on tracheal aspirates drawn before and after TEE. The primary endpoint was the percentage of patients with TEE-associated microaspiration, defined as: (1) ≥ 50% increase in biomarker concentration between pre-TEE and post-TEE samples, and (2) a significant post-TEE biomarker concentration (> 200 μg/L for pepsin and/or > 1685 IU/L for salivary amylase). Secondary endpoints included the development of VAP within three days after TEE and the evolution of tracheal cuff pressure throughout TEE.ResultsWe enrolled 100 patients (35 females), with a median age of 64 (53–72) years. Of the 74 patients analyzed for biomarkers, 17 (23%) got TEE-associated microaspiration. However, overall, pepsin and salivary amylase levels were not significantly different between before and after TEE, with wide interindividual variability. VAP occurred in 19 patients (19%) within 3 days following TEE. VAP patients had a larger tracheal tube size and endured more attempts of TEE probe introduction than their counterparts but showed similar aspiration biomarker concentrations. TEE induced an increase in tracheal cuff pressure, especially during insertion and removal of the probe.ConclusionsWe could not find any association between TEE-associated microaspiration and the development of VAP during the three days following TEE in intubated critically ill patients. However, our study cannot formally rule out a role for TEE because of the high rate of VAP observed after TEE and the limitations of our methods.

International audience; Delayed hemolytic transfusion reaction (DHTR) is an unpredictable severe complication of transfusion in patients with sickle cell disease (SCD). It presents clinically as a vaso-occlusive crisis (VOC), often associated with the failure of one or more organs, after the transfusion of packed red blood cells (pRBC).1,2 Hyperhemolysis is encountered in the most severe forms. Both transfused and autologous red blood cells (RBC) are lysed.The mechanisms underlying DHTR remain unclear. Alloantibodies against RBC antigens were initially thought to underlie the pathophysiology, but no such antibodies are detected in about a third of the cases.3RBC degradation products, such as hemoglobin and heme, are released into the bloodstream during intravascular hemolysis. These elements and heme-loaded membrane microvesicles have recently been implicated in inflammation and organ injury in DHTR.4 Complement is activated via the classical pathway, by alloantibodies, and/or via the alternative pathway, by free heme.5 Hemedependent complement deposits on the endothelium contribute to organ damage.6 Due to these vascular lesions, hyperhemolysis often progresses to multiple organ failure and, in some cases, death.

Hypoxemia is the main feature of COVID-19-related acute respiratory distress syndrome (C-ARDS), but its underlying mechanisms are debated, especially in patients with low respiratory system elastance (Ers). We assessed 60 critically ill patients hospitalized in our intensive care unit for C-ARDS. We used contrast transthoracic echocardiography to assess patent foramen ovale (PFO) shunt and transpulmonary bubble transit (TPBT). The median Ers was 32 cmH2O/L. PFO shunt was detected in six (10%) patients and TPBT in 12 (20%) patients. PFO shunt and TPBT were similar in patients with higher or lower Ers. In conclusion, PFO and TPBT do not seem to be the main drivers of hypoxemia in C-ARDS, especially in patients with lower Ers.

Background Cannabis use is increasing worldwide despite the various health effects of this substance. Methods We report 2 cases of acute hippocampal encephalopathy in heavy cannabis users (>10 joints/d). Results In both male patients, acute encephalitis was suspected. Brain magnetic resonance imaging (MRI) diffusion-weighted sequences showed bilateral high signal abnormalities in hippocampal regions. Patients had renal dysfunction, rhabdomyolysis, and inflammatory syndrome. Investigations showed no evidence of infectious or autoimmune encephalitides. Repeated electroencephalograms revealed no epileptic activity. Clinical, biological, and magnetic resonance imaging acute abnormalities improved within weeks. New exposure to cannabis yielded a new episode of encephalopathy. In both patients, severe long-lasting episodic memory impairment associated with hippocampal atrophy were observed several months later. Conclusions Health professionals should be aware of this cannabis-related syndrome given its severe and long-lasting effects.

Objective: Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay. Methods: A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. Results: The SFAR–SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus. Conclusions: The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy)., SCOPUS: re.j, info:eu-repo/semantics/published

Abbreviations list ATE Arterial Thrombotic Event CHA2DS2VASc Congestive heart failure, Hypertension, Age ≥ 75 (doubled), Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism (doubled), Vascular disease, Age 65 to 74, Sex category (female) HAS-BLED Hypertension, Abnormal renal function, Abnormal liver function, Stroke, Bleeding, Labile INR, Elderly, Drug ICU Intensive Care Unit NOAF New Onset Supraventricular Atrial Fibrillation

Background In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)–almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients. Methods We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 μg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO–almitrine combination. The primary endpoint was the variation of oxygenation (PaO2/FiO2 ratio). Results Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52–72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO2/FiO2 ratio varied from 102 [89–134] mmHg at baseline, to 124 [108–146] mmHg after iNO (p = 0.13) and 180 [132–206] mmHg after iNO and almitrine (p Conclusion In this pilot study of severe C-ARDS patients, iNO–almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiation for patients with cardiogenic shock or cardiac arrest is an attractive strategy since it provides a quick restoration of organ perfusion. One major limitation of VA-ECMO is left ventricle (LV) distension which is associated with poor prognosis. To prevent or treat LV distension, LV decompression may be required. Current strategies for LV decompression have some contraindications, carry a high risk of complications and, for some of them concerns remain regarding their effectiveness. We here describe our experience in two adult patients treated with VA-ECMO in whom indirect LV unloading using pulmonary artery venting was performed for the prevention and the treatment of LV distension, respectively. The placement of the venting cannula in the pulmonary trunk was quick, easy and safe and was associated with the resolution of LV distension. These results suggest that pulmonary artery venting may be an attractive strategy for indirect LV decompression during VA-ECMO.

Background Pneumococcal infections remain the main cause of overwhelming post-splenectomy infections, and purpura fulminans may develop in almost 20% of patients with overwhelming post-splenectomy infection. We aimed at describing the impact of asplenia/hyposplenia on the clinical features and the outcomes of adult patients admitted to the intensive care unit (ICU) for pneumococcal purpura fulminans. Methods A 17-year national multicenter retrospective cohort study included adult patients admitted to 55 French ICUs for an infectious purpura fulminans from 2000 to 2016. Patients with pneumococcal purpura fulminans were analyzed according to the absence or presence of asplenia/hyposplenia. Results Among the 306 patients admitted to the ICU for purpura fulminans, 67 (22%) had a pneumococcal purpura fulminans, of whom 34 (51%) had asplenia (n = 29/34, 85%) or hyposplenia (n = 5/34, 15%) and 33 (49%) had eusplenia. The prevalence of pneumococcal purpura fulminans was seven times higher in asplenic/hyposplenic patients compared to eusplenic patients with purpura fulminans (n = 34/39, 87% vs. n = 33/267, 12%; p n = 25/34, 73% vs. n = 13/33, 39%; p = 0.01). The rate of bacteremia did not differ between asplenic/hyposplenic and eusplenic patients (n = 31/34, 91% vs n = 27/33, 82%; p = 0.261). SAPS II (60 ± 14 vs. 60 ± 18; p = 0.244) and SOFA (13 [1–5] vs. 14 [1–4, 6]; p = 0.48) scores did not differ between asplenic/hyposplenic and eusplenic patients. There were no significant differences between asplenic/hyposplenic and eusplenic patients regarding the rate of limb amputation (n = 9/34, 26% vs. 15/33, 45%; p = 0.11) and hospital mortality (n = 20/34, 59% vs. n = 15/33, 45%; p = 0.27). Conclusions Half of pneumococcal purpura fulminans episodes occurred in asplenic or hyposplenic patients. Pneumococcal vaccine coverage was reported in one third of asplenic/hyposplenic patients. Half of pneumococcal purpura fulminans episodes occurred more than 20 years after splenectomy. Outcomes of pneumococcal purpura fulminans did not show significant differences between patients with or without asplenia or hyposplenia, although the small number of patients included limited our power to detect potential differences between groups.

International audience; Exacerbations are part of the natural history of chronic obstructive pulmonary disease and asthma. Severe exacerbations can cause acute respiratory failure, which may ultimately require mechanical ventilation. This review summarizes practical ventilator strategies for the management of patients with obstructive airway disease. Such strategies include non-invasive mechanical ventilation to prevent intubation, invasive mechanical ventilation, from the time of intubation to weaning, and strategies intended to prevent post-extubation acute respiratory failure. The role of tracheostomy, the long-term prognosis, and potential future adjunctive strategies are also discussed. Finally, the physiological background that underlies these strategies is detailed.

Purpose To explore diagnostic pitfalls and treatment issues in out-of-hospital cardiac arrest of neurological cause (OHCA-NC). Methods Retrospective analysis of all consecutive patients from the Paris Sudden Death Expertise Centre (France) registry from May 2011 to September 2015 presenting with a sustained return of spontaneous circulation (ROSC) at hospital admission and a final diagnosis of OHCA-NC. Description of the early diagnostic check-up performed to identify the cause of cardiac arrest. Logistic multivariate regression to identify factors associated with immediate coronary angiography (iCAG) in OHCA-NC patients. Results Among 3542 patients with ROSC, a final diagnosis of OHCA-NC was established in 247 (7%). The early diagnostic check-up consisted in a total of 207 (84%) immediate cranial CT-scan, 66 (27%) iCAG and 25 (10%) chest CT-scan. The brain CT-scan allowed identifying a neurovascular cause in 116 (47%) patients. An iCAG was performed as the first line exam in 57 (23%) patients, in whom a final diagnosis of neurovascular cause for OHCA-NC was later identified in 41 patients. By multivariate analysis, decision for iCAG was independently associated with ST-segment elevation on post-ROSC electrocardiogram (OR, 5.94; 95%CI, 2.14–18.28; P = 0.0009), whereas an obvious cause of cardiac arrest on scene was negatively associated with iCAG (OR, 0.14; 95%CI, 0.02–0.51; P = 0.01). Conclusions OHCA-NC is a rare event that is mainly related to neurovascular causes. The initial ECG pattern may be a confounder regarding triage for early diagnostic check-up. Further studies are required to explore the potential harmfulness associated with decision to perform an iCAG in this population.

Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416 and was similarly reduced by daily NCX1443 gavage. Compared with WT mice, SAD mice exhibited higher levels of HO-1, endothelial NO synthase, and PDE5 but similar levels of lung cyclic guanosine monophosphate. Cultured pulmonary artery smooth muscle cells from SAD mice grew faster than those from WT mice and had higher PDE5 protein levels. Combining NCX1443 and a PDE5 inhibitor suppressed the growth rate difference between SAD and WT cells and induced a larger reduction in hypoxic PH severity in SAD than in WT mice. By amplifying endogenous protective mechanisms, NCX1443 in combination with PDE5 inhibition may prove useful for treating PH complicating SCD.

Extracorporeal life support could be helpful for severe acute chest syndrome in adults sickle cell disease, because of the frequent hemodynamic compromise in this setting, including acute pulmonary vascular dysfunction and right ventricular failure. The aim of this study was to report the extracorporeal life support experience for severe acute chest syndrome in four referral centers in France.The primary endpoint of this multicentric retrospective study was ICU survival of patients with severe acute chest syndrome managed with extracorporeal life support. Secondary endpoints included comparisons between survivors and nonsurvivors.We performed this study between January 2009 and July 2017 in four referral centers in France.We included adult patients (age18 yr) with sickle cell disease, admitted for severe acute chest syndrome and who required extracorporeal life support during the ICU stay.The study was observational.Over the 8-year period, 22 patients with sickle cell disease required extracorporeal life support for severe acute chest syndrome, including 10 (45%) veno-venous and 12 (55%) veno-arterial extracorporeal life support. In-ICU mortality was high (73%). Nonsurvivors had a higher severity at extracorporeal life support implantation, as assessed by their Vasoactive-Inotrope Score and number of organ failures.Our study shows that outcome is impaired in sickle cell disease patients receiving extracorporeal life support while in severe multiple organ failure. Further studies are needed to evaluate selection criteria in this setting.

Rationale In a recent systematic review, aging has been identified as the only factor independently associated with mortality during human acute respiratory distress syndrome (ARDS). We explored this age-dependent severity in a clinically relevant double hit murine ARDS model. Methods Young adult (Y, 10–12 weeks) and middle-old (O, 12–13 months) male C57BL6 mice underwent an aspiration of Escherichia coli lipopolysaccharide (LPS) or control saline vehicle. Twenty hours later, four groups of mice were sacrificed [Y (control) , O (control) , Y (LPS) and O (LPS) ]. Four other groups of mice underwent 3 h of low tidal volume (8 mL/kg) mechanical ventilation (MV) [Y (MV) , O (MV) , Y (LPS + MV) and O (LPS + MV) ]. Lung mechanics were assessed hourly during MV. Right ventricular pressure and cardiac output were measured at the end of the MV. After sacrifice, lung inflammation, edema and injury were explored with bronchoalveolar lavage (BAL) and histology. Results After saline aspiration, middle-old mice had a higher respiratory system compliance than young adult mice. LPS aspiration dramatically altered the baseline compliance in middle-old (O (LPS) ), but not in young adult (Y (LPS) ) mice. Middle-old mice had a more pronounced alteration in lungs mechanics during MV as compared to young adult mice. Lung inflammation (as assessed by the total cell count, IL-6, TNFα and MIP-2 concentrations in BAL fluid), systemic inflammation (as assessed by plasma IL-6 concentration) and alveolocapillary leak (as assessed by the total protein concentration of BAL fluid) were higher in O (LPS) and O (LPS + MV) mice as compared to Y (LPS) and Y (LPS + MV) mice, respectively. The combination of LPS + MV induced a higher lung injury as compared to LPS alone in middle-old mice but not in young adult mice. Hemodynamics (systemic blood pressure, cardiac output and pulmonary vascular resistances) were similar between Y (MV) and O (MV) on the one hand and between Y (LPS + MV) and O (LPS + MV) on the other hand. Conclusion Middle-old mice were more susceptible to both LPS alone and the combination of LPS and low tidal volume MV as compared to their young adult counterparts. The synergism between LPS and MV was amplified in middle-old mice.

BACKGROUND Red blood cell (RBC) storage in blood banks is not exempt from cellular injury. Alterations not observed on RBCs freshly isolated from units can rapidly appear in circulation. The transfusion of old blood units, even if this is a controversial issue, could therefore have adverse effects on the recipient. We wanted to determine the respective effects of storage duration and recipient plasma on RBCs for transfusion into patients with severe sepsis. STUDY DESIGN AND METHODS Eleven stored RBC units were sampled at various time points, approximately Days 3 to 8 (referred to as fresh RBCs) and Days 38 to 42 (old RBCs) and tested in coincubation experiments with plasma obtained from 13 patients with severe sepsis and 17 healthy donors as controls. RBCs were tested after 24 or 48 hours at 37°C for the detection of senescence markers (phosphatidylserine exposure, calcium influx, and reactive oxygen species detection and decrease in size) with or without exposure to plasma. RESULTS We confirmed that a 42-day refrigerated storage of RBCs alone (without any incubation in plasma) had no significant effect on RBCs and no senescence marker detected. By contrast, ex vivo exposure to plasma samples altered both fresh and old RBCs, with a much larger effect for old RBCs, regardless of the plasma used (sepsis vs. control). CONCLUSION We show that the main factor affecting the senescence of RBCs for transfusion into patients with severe sepsis is the age of the stored units rather than the clinical status of the recipient.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.

Relative adrenal insufficiency (RAI) is common in intensive care unit patients, particularly during septic shock (SS). Cardiogenic shock (CS) may share some pathophysiological features with SS. The aim of this study was to evaluate the prevalence and long-term prognosis of RAI during CS.Prospective observational study conducted in the intensive care and cardiology units in one university hospital in France. Patients meeting the criteria for CS without prior corticosteroid therapy were included. Total blood cortisol levels were assessed immediately before (T0) a short corticotropin stimulation test (0.25 mg i.v. of tetracosactrin) and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0.Of the 92 patients enrolled, 42 (46%) (95% confidence interval [CI] [36%-56%]) died in hospital and 7 more died during a median follow-up of 616 [57-2,498] days, for an overall mortality rate of 53% (95% CI [43%-63%]). Three groups were identified based on the corticotropin test: group 1 (T0 ≤798 nmol/L and Δmax473 nmol/L), group 2 ([T0798 nmol/L and Δmax473 nmol/L] or [T0 ≤798 nmol/L and Δmax ≤473 nmol/L]), and group 3 (T0798 nmol/L and Δmax ≤473 nmol/L) with an overall survival of 76%, 43%, and 15%, respectively (log rank P = 0.003). In the multivariable analysis, adrenal nonresponse (group 3) was an independent predictor of mortality (P = 0.04), along with left ventricular ejection fraction, Simplified Acute Physiology Score II, and cardiac arrest.These data suggest that a short corticotropin test has a good prognostic value in CS and allows identifying patients at higher risk of death.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).