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Abstract Background Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including bla CTX-M, the most common ESBL-encoding gene. Methods This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: bla CTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and bla CTX-M were concordant in 35/41 (85%) episodes, and in all episodes where bla CTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion mPCR bla CTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Abstract Background During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. Methods This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. Results 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. Conclusion This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Abstract Background Left atrial strain (LAS) is a measure of atrial wall deformation during cardiac cycle and reflects atrial contribution to cardiovascular performance. Pathophysiological significance of LAS in critically ill patients with hemodynamic instability has never been explored. This study aimed at describing LAS and its variation during volume expansion and to assess the relationship between LAS components and fluid responsiveness. Methods This prospective observational study was performed in a French ICU and included patients with acute circulatory failure, for whom the treating physician decided to proceed to volume expansion (rapid infusion of 500 mL of crystalloid solution). Trans-thoracic echocardiography was performed before and after the fluid infusion. LAS analysis was performed offline. Fluid responsiveness was defined as an increase in velocity-time integral (VTI) of left ventricular outflow tract ≥ 10%. Results Thirty-eight patients were included in the final analysis. Seventeen (45%) patients were fluid responders. LAS analysis had a good feasibility and reproducibility. Overall, LAS was markedly reduced in all its components, with values of 19 [15 – 32], -9 [-19 – -7] and − 9 [-13 – -5] % for LAS reservoir (LASr), conduit (LAScd) and contraction (LASct), respectively. LASr, LAScd and LASct significantly increased during volume expansion in the entire population. Baseline value of LAS did not predict fluid responsiveness and the changes in LAS and VTI during volume expansion were not significantly correlated. Conclusions LAS is severely altered during acute circulatory failure. LAS components significantly increase during fluid administration, but cannot be used to predict or assess fluid responsiveness.

Abstract Background Multiple devices are available for noninvasive oxygenation support, including non-rebreather oxygen mask (O2-mask), high-flow oxygen through nasal cannula (HFNC), continuous positive airway pressure (CPAP), mask noninvasive ventilation (Mask-NIV) and helmet NIV (Helmet-NIV). As tidal volume is a key determinant of efficacy and safety during ventilatory support, we assessed whether it was influenced by the type of noninvasive oxygenation device. Methods A bench study using a manikin with a realistic face connected to a lung simulator was performed. Six conditions were assessed: no device, O2-mask, HFNC, CPAP, Mask-NIV and Helmet-NIV. Three respiratory mechanics were simulated (normal, obstructive, restrictive), at three simulated efforts (low, moderate, respiratory distress). Flow was recorded at the lung simulator inlet and mouth pressure into the manikin mouth. The same devices were evaluated on healthy volunteers with tidal volume assessed by electrical impedance tomography (EIT). Results Tidal volume was significantly influenced by oxygenation devices in bench model. As compared to O2-mask, HFNC and CPAP delivered significantly lower tidal volumes (440 ± 352 mL, 414 ± 333 mL and 377 ± 297 mL, respectively), while Mask-NIV or Helmet-NIV were associated with significantly higher tidal volumes (690 ± 321 mL and 652 ± 366 mL, respectively). Tidal volume was strongly correlated with the specific effect of each device on mouth pressure during inspiration: HFNC and CPAP were characterized by a negative PTPmouth (− 0.3 [− 0.8 to − 0.2] and − 0.7 [− 2.2 to − 0.5] cmH2O.sec/cycle, respectively), while Helmet-NIV and Mask-NIV were associated with a positive PTPmouth (4.5 [4.1–4.6] and 6.1 [5.9–7.1] cmH2O.sec/cycle, respectively). Tidal volume was also significantly influenced by oxygenation devices in healthy volunteers, with similar tidal volumes between O2-mask and CPAP (644 [571–764] and 648 [586–770] mL) but higher with HFNC, Mask-NIV and Helmet-NIV (819 [609–918], 1110 [661–1305] and 1086 [833–1243] mL). Conclusions Tidal volume is significantly influenced by noninvasive oxygenation support devices, with a strong correlation with the pressure variation generated into the mouth during inspiration. NIV was associated with the highest tidal volumes and CPAP with the lowest ones. Clinical studies are needed to clarify the clinical implications of these effects.

Abstract Background Acute myocardial infarction (AMI) is one of the major cardiac complications in patients hospitalized in the intensive care unit (ICU) for non-cardiac disease. A better knowledge of ischemic and bleeding risks in these patients is needed to identify those most likely to benefit from specific cardiac management. We therefore assessed the incidence and predictors of a composite outcome of severe ischemic event (AMI recurrence, ischemic stroke), major bleeding, or all-cause death in this setting. Methods In this multicenter retrospective study, all consecutive adult patients admitted for non-cardiac disease to four French university hospital ICUs between January 2012 and December 2018 who had an AMI with obstructive coronary artery disease (OCAD) during the ICU stay were considered for inclusion. AMI with OCAD was defined as an elevated cardiac troponin value associated with at least one sign (clinical, electrocardiographic, or echocardiographic) suggestive of myocardial ischemia and presence of OCAD on coronary angiography. The primary endpoint was in-hospital occurrence of the composite outcome. Results Ninety-six patients [median age 69 years, 22 women (23%), 59 with sepsis (61%), 35 with ST elevation (37%), median sequential organ failure assessment (SOFA) of 8 on the day of AMI] were included. The median peak cardiac troponin value was 131 (IQR 44–303) times the upper reference limit. Dual antiplatelet, therapeutic anticoagulation, and early mechanical reperfusion therapies were administered in 61 (64%), 68 (71%), and 47 (49%) patients, respectively. The composite outcome occurred in 48 (50%) patients. Severe ischemic events occurred in 17 (18%) patients and major bleeding in 26 (27%) patients; 26 patients (27%) died in the hospital. AMI management was not significantly different in patients with and without the composite outcome. A history of arterial hypertension (HR 2.05, 95% CI 1.01–4.16) and high SOFA score at the time of AMI (HR 1.07, 95% CI 1.00–1.15) were independent risk factors for the composite outcome. Conclusions Patients who have an AMI with OCAD during an ICU stay for non-cardiac disease are at risk of a composite outcome of severe ischemia, major bleeding, and death. A history of arterial hypertension and high SOFA scores were independent hazards for poor prognosis. Graphical Abstract

Abstract Background Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. Results The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as “BA.2” (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as “BA.4/BA.5”, and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as “BQ.1.1”. The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. Conclusions Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.

Abstract Background Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. Methods Multicentre, retrospective cohort study conducted in France. Results From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). Conclusions Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Abstract Background The implantation of venovenous extracorporeal membrane oxygenation (VV-ECMO) support to manage severe acute respiratory distress syndrome generates large variations in carbon dioxide partial pressure (PaCO2) that are associated with intracranial bleeding. We assessed the feasibility and efficacy of a pragmatic protocol for progressive dual titration of sweep gas flow and minute ventilation after VV-ECMO implantation in order to limit significant PaCO2 variations. Patients and methods A protocol for dual titration of sweep gas flow and minute ventilation following VV-ECMO implantation was implemented in our unit in September 2020. In this single-centre retrospective before-after study, we included patients who required VV-ECMO from March, 2020 to May, 2021, which corresponds to two time periods: from March to August, 2020 (control group) and from September, 2020 to May, 2021 (protocol group). The primary endpoint was the mean absolute change in PaCO2 in consecutive arterial blood gases samples drawn over the first 12 h following VV-ECMO implantation. Secondary endpoints included large (> 25 mmHg) initial variations in PaCO2, intracranial bleedings and mortality in both groups. Results Fifty-one patients required VV-ECMO in our unit during the study period, including 24 in the control group and 27 in the protocol group. The protocol was proved feasible. The 12-h mean absolute change in PaCO2 was significantly lower in patients of the protocol group as compared with their counterparts (7 mmHg [6–12] vs. 12 mmHg [6–24], p = 0.007). Patients of the protocol group experienced less large initial variations in PaCO2 immediately after ECMO implantation (7% vs. 29%, p = 0.04) and less intracranial bleeding (4% vs. 25%, p = 0.04). Mortality was similar in both groups (35% vs. 46%, p = 0.42). Conclusion Implementation of our protocol for dual titration of minute ventilation and sweep gas flow was feasible and associated with less initial PaCO2 variation than usual care. It was also associated with less intracranial bleeding.

Abstract Background Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. Methods We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. Results The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score

Abstract Background Necrotizing skin and soft tissue infections (NSTIs) are rare but serious and rapidly progressive infections characterized by necrosis of subcutaneous tissue, fascia and even muscle. The care pathway of patients with NSTIs is poorly understood. A better characterization of the care trajectory of these patients and a better identification of patients at risk of a complicated evolution, requiring prolonged hospitalization, multiple surgical re-interventions, or readmission to the intensive care unit (ICU), is an essential prerequisite to improve their care. The main objective of this study is to obtain large-scale data on the care pathway of these patients. We performed a retrospective multicenter observational cohort study in 13 Great Paris area hospitals, including patients hospitalized between January 1, 2015 and December 31, 2019 in the ICU for surgically confirmed NSTIs. Results 170 patients were included. The median duration of stay in ICU and hospital was 8 (3–17) and 37 (14–71) days, respectively. The median time from admission to first surgical debridement was 1 (0–2) day but 69.9% of patients were re-operated with a median of 1 (0–3) additional debridement. Inter-hospital transfer was necessary in 52.4% of patients. 80.2% of patients developed organ failures during the course of ICU stay with 51.8% of patients requiring invasive mechanical ventilation, 77.2% needing vasopressor support and 27.7% renal replacement therapy. In-ICU and in-hospital mortality rates were 21.8% and 28.8%, respectively. There was no significant difference between patients with abdomino-perineal NSTIs (n = 33) and others (n = 137) in terms of in-hospital or ICU mortality. Yet, immunocompromised patients (n = 43) showed significantly higher ICU and in-hospital mortality rates than non-immunocompromised patients (n = 127) (37.2% vs. 16.5%, p = 0.009, and 53.5% vs. 20.5%, p

Abstract Background β-lactams are the main antibiotics used against wild-type AmpC-producing Enterobacterales (wtAE). However, they may fail or select AmpC-overproducing mutants. Our aim was to assess factors associated with clinical failure of β-lactams in the treatment of wtAE infection. Methods From September 2017 to December 2020, we prospectively included all consecutive patients treated by definitive β-lactams therapy for wtAE infection in four university ICUs. Clinical failure was defined as inadequate response to antimicrobial therapy leading to death or to the switch for a broader-spectrum antibiotic. Results 177 patients were included and 29.4% progressed to clinical failure. E. cloacae was the most prevalent species (42.4%) and ventilator-associated pneumonia (VAP) was the most frequent wtAE infection (69.5%). Cefepime and cefotaxime were used as definitive antibiotic treatment in 42.9% and 27.7% of patients, respectively. Occurrence of AmpC-overproduction was documented in 5.6% of patients and was associated with clinical failure (p = 0.004). In multivariate analysis, VAP (p

Abstract Background Intensive care unit (ICU) patients often endure discomfort and distress brought about by their medical environment and the subjective experience of their stay. Distress, pain, and loss of control are important predictors of future neuropsychiatric disorders. Depression, anxiety, and post-traumatic stress are common after discharge. We aimed at mitigating acute stress and discomfort via a novel intervention based on body image rehabilitation and rehabilitation of senses performed following a holistic approach guided by positive communication (corporeal rehabilitation care, CRC). Results We conducted a prospective observational study on 297 consecutively enrolled patients participating in at least one CRC session. Benefits of CRC were assessed on both subjective analogical scales of stress, pain, and well-being criteria, and objective clinical measures of dyspnea, respiratory rate, and systolic arterial pressure, just after CRC and long after (a median of 72 min later) to estimate its remote effect. Results showed that CRC had a positive effect on all overt measures of distress (acute stress, pain, discomfort) just after CRC and remotely. This beneficial effect was also observed on dyspnea and respiratory rate. Results also showed that best CRC responders had higher baseline values of stress and heart rate and lower baseline values of well-being score, indicating that the care targeted the population most at risk of developing psychological sequelae. Interestingly, a positive CRC response was associated with a better survival even after adjustment for physiologic severity, indicating a potential to identify patients prompt to better respond to other therapeutics and/or rehabilitation. Conclusion This study demonstrated the feasibility of an innovative holistic patient-centered care approach and its short-term positive effects on critical parameters that are considered risk factors for post-intensive care syndrome. Further studies are warranted to study long-term benefits for patients, and overall benefits for relatives as well as ICU staff.

Abstract Background Ineffective triggering is frequent during pressure support ventilation (PSV) and may persist despite ventilator adjustment, leading to refractory asynchrony. We aimed to assess the effect of proportional assist ventilation with load-adjustable gain factors (PAV+) on the occurrence of refractory ineffective triggering. Design Observational assessment followed by prospective cross-over physiological study. Setting Academic medical ICU. Patients Ineffective triggering was detected during PSV by a twice-daily inspection of the ventilator’s screen. The impact of pressure support level (PSL) adjustments on the occurrence of asynchrony was recorded. Patients experiencing refractory ineffective triggering, defined as persisting asynchrony at the lowest tolerated PSL, were included in the physiological study. Interventions Physiological study: Flow, airway, and esophageal pressures were continuously recorded during 10 min under PSV with the lowest tolerated PSL, and then under PAV+ with the gain adjusted to target a muscle pressure between 5 and 10 cmH2O. Measurements Primary endpoint was the comparison of asynchrony index between PSV and PAV+ after PSL and gain adjustments. Results Among 36 patients identified having ineffective triggering under PSV, 21 (58%) exhibited refractory ineffective triggering. The lowest tolerated PSL was higher in patients with refractory asynchrony as compared to patients with non-refractory ineffective triggering. Twelve out of the 21 patients with refractory ineffective triggering were included in the physiological study. The median lowest tolerated PSL was 17 cmH2O [12–18] with a PEEP of 7 cmH2O [5–8] and FiO2 of 40% [39–42]. The median gain during PAV+ was 73% [65–80]. The asynchrony index was significantly lower during PAV+ than PSV (2.7% [1.0–5.4] vs. 22.7% [10.3–40.1], p

Abstract 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.

Abstract 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 (T 0) 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 T 0. CIRCI was defined as T 0

Abstract Background We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter (“Filter Frugal CPAP”, FF-CPAP) in and out the ICU. Methods (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. Results Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient’s work of breathing (6–34%) needed to sustain the tidal volume, depending on the filter’s resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p

Abstract 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

Abstract 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).

Abstract 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.

Abstract Background Necrotizing skin and soft tissue infections (NSTIs) require both prompt medical and surgical treatment. The coordination of multiple urgent interventions by care bundles has improved outcome in other settings. This study aimed to assess the impact of a multidisciplinary care bundle on management and outcome of patients with NSTIs. Methods Patients with NSTIs admitted between 2006 and 2017 were compared according to admission before or after bundle implementation (2012–2013). This bundle consisted mainly in (1) the creation of a multidisciplinary task force; (2) management guidelines on empirical antibiotics, intensive care unit admission criteria, a triage algorithm to accelerate operating room access; and (3) an active communication policy. Patient recruitment and management were compared between pre- and post-implementation periods. Main outcome was day 60-censored hospital survival. Results Overall, 224 patients were admitted: 60 before, 35 during, and 129 after bundle implementation. Admission after implementation was associated with increased yearly admissions (10 [8–13] vs 30 [24–43] patients/year, p = 0.014) and decreased mortality (30 vs 15%, HR = 0.49 [0.26–0.92]; p = 0.026) but was no longer a protective factor for mortality after adjustment on confounding factors (adjusted HR = 0.90 [0.43–1.88], p = 0.780). There was no significant difference regarding time to surgery (0 [0–1] vs 0 [0–1] days, p = 0.192) or rate of antibiotic treatment within 24 h (98% vs 99%, p > 0.99). Conclusions Implementation of a multidisciplinary care bundle for NSTIs was feasible, but in a retrospective study from an already experienced center was not associated with significantly increased survival after adjustment.

Abstract 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

Abstract Background Pleural effusion is common during invasive mechanical ventilation, but its role during weaning is unclear. We aimed at assessing the prevalence and risk factors for pleural effusion at initiation of weaning. We also assessed its impact on weaning outcomes and its evolution in patients with difficult weaning. Methods We performed a prospective multicenter study in five intensive care units in France. Two hundred and forty-nine patients were explored using ultrasonography. Presence of moderate-to-large pleural effusion (defined as a maximal interpleural distance ≥ 15 mm) was assessed at weaning start and during difficult weaning. Results Seventy-three (29%) patients failed weaning, including 46 (18%) who failed the first spontaneous breathing trial (SBT) and 39 (16%) who failed extubation. Moderate-to-large pleural effusion was detected in 81 (33%) patients at weaning start. Moderate-to-large pleural effusion was associated with more failures of the first SBT [27 (33%) vs. 19 (11%), p

Abstract Background Cardiac dysfunction is a common cause of weaning failure. Weaning shares some similarities with a cardiac stress test and may challenge active phases of the cardiac cycle-like ventricular contractility and relaxation. This study aimed at assessing systolic and diastolic function during the weaning process and scrutinizing their dynamics during weaning trials. Methods Echocardiography was performed during baseline ventilator settings to assess cardiac function at the initiation of the weaning process and at the start and the end of consecutive weaning trials (performed at day-1, day-2, and before extubation if applicable) to explore the evolution of left ventricle contractility and relaxation in a subset of patients. Results Among 67 patients included, weaning was prolonged (≥ 7 days) in 18 (27%) patients and short (

Abstract Background We assessed prevalence, associated factors and prognosis of extended-spectrum beta-lactamase-producing Enterobacteriaceae pneumonia acquired in intensive care unit (ESBL-PE pneumonia) among carriers. Variables associated with nosocomial pneumonia caused by carbapenem-resistant bacteria (CRB) were also assessed. Methods A 6-year prospective study (May 2009–March 2015) in the medical ICU of an 850-bed university-affiliated hospital was conducted. Results Of the 6303 patients admitted, 843 (13.4%) had ESBL-PE carriage detected. Among carriers, 111 (13%) patients developed ICU-acquired pneumonia of whom 48 (43%) had ESBL-PE pneumonia (6% of carriers). By multivariable analysis, SAPS II at admission >43 [OR 2.81 (1.16–6.79)] and colonization with Enterobacter sp. or K. pneumoniae species [OR 10.96 (2.93–41.0)] were independent predictive factors for ESBL-PE pneumonia in colonized patients, whereas receipt of >2 days of amoxicillin/clavulanic acid during the ICU stay [OR 0.24 (0.08–0.71)] was protective. Patients with ESBL-PE pneumonia had a higher SOFA score (p = 0.037) and more frequent septic shock at pneumonia onset (p = 0.047). However, ESBL-PE pneumonia was not an independent predictor of mortality. Twenty-five patients had pneumonia caused by CRB. Chronic renal insufficiency, administration of third-generation cephalosporin within the past 3 months, acute respiratory distress syndrome before pneumonia and prior therapy with a carbapenem or fluoroquinolones were associated with CRB pneumonia in this selected population. Conclusions Although few ESBL-PE carriers developed ESBL-PE pneumonia overall, a high proportion of pneumonia were caused by ESBL-PE in carriers developing ICUAP. ESBL-PE pneumonia was not an independent predictor of mortality. As pneumonia caused by CRB is increasing, knowledge of factors associated with ESBL-PE or CRB pneumonia may help empiric therapy of pneumonia among ESBL-PE carriers.

Abstract Background Patients meeting the Berlin definition for the acute respiratory distress syndrome (ARDS) might lack exposure to one or more “common” risk factors and exhibit different clinical phenotype and outcomes. We aimed to compare the clinical presentation and outcome of ARDS patients with or without risk factors, the impact on hospital mortality, and to assess the diagnostic work-up performed. The current study is an ancillary analysis of an international, multicenter, prospective cohort study (the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure, LUNG SAFE). Patients meeting ARDS criteria within 2 days of acute hypoxemic respiratory failure onset were included in the study and categorized as having risk factors or not. Outcomes were compared using propensity score matching. Results Among 2813 patients, 234 (8.3% [7.3–9.3]) had no ARDS risk factor identified. These were older, had more frequent chronic diseases and presented with less severe SOFA and non-pulmonary SOFA scores (p 0.99). Among ARDS with no risk factor, 45 patients (19.2%) had a specific diagnosis made. As compared to others, patients having ARDS with no risk factor had a lower ICU but not hospital mortality (34.6 vs 40.0%; p = 0.12). A matched cohort analysis confirmed the lack of significant difference in mortality. Conclusion Eight percent of ARDS patients have no identified risk factor, 80% of whom have no etiological diagnosis made. The outcome of ARDS with no risk factor was comparable to other ARDS but few had a comprehensive diagnostic work-up, potentially leading to missed curable diseases. Trial registration clinicaltrials.gov Identifier: NCT02010073

Abstract Background The influence of socioeconomic deprivation on health inequalities is established, but its effect on critically ill patients remains unclear, due to inconsistent definitions in previous studies. Methods Prospective multicenter cohort study conducted from March to June 2018 in eight ICUs in the Greater Paris area. All admitted patients aged ≥ 18 years were enrolled. Socioeconomic phenotypes were identified using hierarchical clustering, based on education, health insurance, income, and housing. Association of phenotypes with 180-day mortality was assessed using Cox proportional hazards models. Results A total of 1,748 patients were included. Median age was 62.9 [47.4–74.5] years, 654 (37.4%) patients were female, and median SOFA score was 3 [1–6]. Study population was clustered in five phenotypes with increasing socioeconomic deprivation. Patients from phenotype A (n = 958/1,748, 54.8%) were without socioeconomic deprivation, patients from phenotype B (n = 273/1,748, 15.6%) had only lower education levels, phenotype C patients (n = 117/1,748, 6.7%) had a cumulative burden of 1[1–2] deprivations and all had housing deprivation, phenotype D patients had 2 [1–2] deprivations, all of them with income deprivation, and phenotype E patients (n = 93/1,748, 5.3%) included patients with 3 [2–4] deprivations and included all patients with health insurance deprivation. Patients from phenotypes D and E were younger, had fewer comorbidities, more alcohol and opiate use, and were more frequently admitted due to self-harm diagnoses. Patients from phenotype C (predominant housing deprivation), were more frequently admitted with diagnoses related to chronic respiratory diseases and received more non-invasive positive pressure ventilation. Following adjustment for age, sex, alcohol and opiate use, socioeconomic phenotypes were not associated with increased 180-day mortality: phenotype A (reference); phenotype B (hazard ratio [HR], 0.85; 95% confidence interval CI 0.65–1.12); phenotype C (HR, 0.56; 95% CI 0.34–0.93); phenotype D (HR, 1.09; 95% CI 0.78–1.51); phenotype E (HR, 1.20; 95% CI 0.73–1.96). Conclusions In a universal health care system, the most deprived socioeconomic phenotypes were not associated with increased 180-day mortality. The most disadvantaged populations exhibit distinct characteristics and medical conditions that may be addressed through targeted public health interventions.

Abstract Background Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching. Results 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p

Abstract Background Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. Results We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p

Abstract Background Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.

Abstract Background Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. Methods Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m−2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 5 points and respiratory primary failure as reason for admission. Conclusions Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov )

Abstract Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1 + or 1 −); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2 + or 2 −); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP > 5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.

Abstract Background Intubation and extubation of ventilated patients are not risk-free procedures in the intensive care unit (ICU) and can be associated with morbidity and mortality. Intubation in the ICU is frequently required in emergency situations for patients with an unstable cardiovascular or respiratory system. Under these circumstances, it is a high-risk procedure with life-threatening complications (20–50%). Moreover, technical problems can also give rise to complications and several new techniques, such as videolaryngoscopy, have been developed recently. Another risk period is extubation, which fails in approximately 10% of cases and is associated with a poor prognosis. A better understanding of the cause of failure is essential to improve success procedure. Results and conclusion In constructing these guidelines, the SFAR/SRLF experts have made use of new data on intubation and extubation in the ICU from the last decade to update existing procedures, incorporate more recent advances and propose algorithms.