Hyper-inflammatory profile and immunoparalysis in patients with severe Legionnaires' disease.

Introduction: Severe Legionnaires' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity. Methods: A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8. Results: Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-ß, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status. Discussion: The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.

Outcome and factors associated with mortality in patients receiving urgent chemotherapy in the ICU: A retrospective study.

PURPOSE: This study aimed to assess the outcome and factors associated with mortality in patients who received urgent chemotherapy (CT) in the intensive care unit (ICU) in Lyon, France. MATERIAL AND METHODS: A total of 147 adult patients diagnosed with cancer and requiring urgent CT during ICU stay between October 2014 and December 2019 were included in this retrospective study. RESULTS: Hematological cancer was found in 77% of patients, and acute respiratory failure was the leading cause of ICU admission (46.3%). The 6-month mortality rate was 69.4%; patients with solid cancer had a higher risk of mortality. Patients who died within 6 months had a poor performance score and a higher SOFA score at admission. The multivariate analysis showed that solid tumors, sepsis on the day of CT, and SOFA score on the day of CT were associated with 6-month mortality. Additionally, 95% of patients who survived the ICU resumed conventional CT, with a higher likelihood of resuming CT among those with hematological cancer. CONCLUSION: Urgent CT in the ICU is feasible in a specific subset of patients, mainly those with hematological cancer, with resumption of the curative treatment regimen after ICU discharge.

Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study.

PURPOSE: The impact of immunosuppression on intensive care unit (ICU)-acquired colonization and infection related to multidrug-resistant (MDR) bacteria (ICU-MDR-col and ICU-MDR-inf, respectively) is unknown. METHODS: We carried out an observational prospective cohort study in 8 ICUs in France (all with single-bed rooms and similar organizational characteristics). All consecutive patients with an ICU stay > 48 h were included, regardless of immune status, and followed for 28 days. Patients underwent systematic screening for colonization with MDR bacteria upon admission and every week subsequently. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, solid-organ transplant, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic. The primary endpoint was the incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. RESULTS: 750 patients (65.9% males, median age 65 years) were included, among whom 264 (35.2%) were immunocompromised. Reasons for ICU admission, severity scores and exposure to invasive devices and antibiotics during ICU stay were comparable between groups. After adjustment for center and pre-specified baseline confounders, immunocompromised patients had a lower incidence rate of ICU-MDR-col and/or ICU-MDR-inf (adjusted incidence ratio 0.68, 95% CI 0.52-0.91). When considered separately, the difference was significant for ICU-MDR-col, but not for ICU-MDR-inf. The distribution of MDR bacteria was comparable between groups, with a majority of Enterobacteriacae resistant to third-generation cephalosporins (~ 74%). CONCLUSION: Immunocompromised patients had a significantly lower incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. This finding points to the role of contact precautions and isolation measures, and could have important implications on antibiotic stewardship in this population.

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-debridement Antibiotic Treatment for 10 versus 20 days.

BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.

A retrospective comparison of COVID-19 and seasonal influenza mortality and outcomes in the ICUs of a French university hospital.

BACKGROUND: SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019. OBJECTIVE: To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France. DESIGN: A retrospective study. SETTING: Six ICUs in a single institution in Lyon, France. PATIENTS: Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021. MAIN OUTCOMES AND MEASURES: Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model. RESULTS: COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement. CONCLUSION: After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

Non-invasive quantification of acute macrophagic lung inflammation with [11C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome.

PURPOSE: Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of [11C](R)-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues. MATERIAL AND METHODS: We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BPND) were compared to lung macrophage presence, semi-quantified in pathology. RESULTS: The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BPND determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BPND (p = 0.03). Regional BPND was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03). CONCLUSION: To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [11C](R)-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.

IMPACT OF DIFFERENT VENTILATION STRATEGIES ON GAS EXCHANGES AND CIRCULATION DURING PROLONGED MECHANICAL CARDIO-PULMONARY RESUSCITATION IN A PORCINE MODEL.

ABSTRACT: Background: Optimal ventilation during cardio-pulmonary resuscitation (CPR) is still controversial. Ventilation is expected to provide sufficient arterial oxygen content and adequate carbon dioxide removal, while minimizing the risk of circulatory impairment. The objective of the present study was to compare three ventilation strategies in a porcine model during mechanical continuous chest compressions (CCC) according to arterial oxygenation and hemodynamic impact. Method: Ventricular fibrillation was induced and followed by five no-flow minutes and thirty low-flow minutes resuscitation with mechanical-CCC without vasopressive drugs administration. Three groups of eight Landras pig were randomized according to the ventilation strategy: 1. Standard nonsynchronized volume-control mode (SD-group); 2. synchronized bilevel pressure-controlled ventilation (CPV-group); 3. continuous insufflation with Boussignac Cardiac-Arrest Device (BC-group). We assessed 1. arterial blood gases, 2. macro hemodynamics, 3. tissular cerebral macro and micro-circulation and 4. airway pressure, minute ventilation at baseline and every 5 minutes during the protocol. Results: Arterial PaO2 level was higher at each measurement time in SD-group (>200 mm Hg) compare to CPV-group and BC-group ( P < 0.01). In BC-group, arterial PaCO2 level was significantly higher (>90mm Hg) than in SD and CPV groups ( P < 0.01). There was no difference between groups concerning hemodynamic parameters, cerebral perfusion and microcirculation. Conclusion: Ventilation modalities in this porcine model of prolonged CPR influence oxygenation and decarboxylation without impairing circulation and cerebral perfusion. Synchronized bi-level pressure-controlled ventilation' use avoid hyperoxia and was as efficient as asynchronized volume ventilation to maintain alveolar ventilation and systemic perfusion during prolonged CPR.

Improving motion-mask segmentation in thoracic CT with multiplanar U-nets.

PURPOSE: Motion-mask segmentation from thoracic computed tomography (CT) images is the process of extracting the region that encompasses lungs and viscera, where large displacements occur during breathing. It has been shown to help image registration between different respiratory phases. This registration step is, for example, useful for radiotherapy planning or calculating local lung ventilation. Knowing the location of motion discontinuity, that is, sliding motion near the pleura, allows a better control of the registration preventing unrealistic estimates. Nevertheless, existing methods for motion-mask segmentation are not robust enough to be used in clinical routine. This article shows that it is feasible to overcome this lack of robustness by using a lightweight deep-learning approach usable on a standard computer, and this even without data augmentation or advanced model design. METHODS: A convolutional neural-network architecture with three 2D U-nets for the three main orientations (sagittal, coronal, axial) was proposed. Predictions generated by the three U-nets were combined by majority voting to provide a single 3D segmentation of the motion mask. The networks were trained on a database of nonsmall cell lung cancer 4D CT images of 43 patients. Training and evaluation were done with a K-fold cross-validation strategy. Evaluation was based on a visual grading by two experts according to the appropriateness of the segmented motion mask for the registration task, and on a comparison with motion masks obtained by a baseline method using level sets. A second database (76 CT images of patients with early-stage COVID-19), unseen during training, was used to assess the generalizability of the trained neural network. RESULTS: The proposed approach outperformed the baseline method in terms of quality and robustness: the success rate increased from 53 % to 79 % without producing any failure. It also achieved a speed-up factor of 60 with GPU, or 17 with CPU. The memory footprint was low: less than 5 GB GPU RAM for training and less than 1 GB GPU RAM for inference. When evaluated on a dataset with images differing by several characteristics (CT device, pathology, and field of view), the proposed method improved the success rate from 53 % to 83 % . CONCLUSION: With 5-s processing time on a mid-range GPU and success rates around 80 % , the proposed approach seems fast and robust enough to be routinely used in clinical practice. The success rate can be further improved by incorporating more diversity in training data via data augmentation and additional annotated images from different scanners and diseases. The code and trained model are publicly available.

Validation of a novel system to assess end-expiratory lung volume and alveolar recruitment in an ARDS model.

BACKGROUND: Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin-washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELVMBNW), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELVMBNW, using CT as the gold standard. RESULTS: Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH2O. EELV was computed at each PEEP step by both the MBNW technique (EELVMBNW) and CT (EELVCT). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (VrecCT), and computed from EELV measurements (VrecMBNW) as ΔEELV minus the product of ΔPEEP by static compliance. EELVMBNW and EELVCT were significantly correlated (R2 = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELVMBNW and EELVCT was: EELVMBNW = 0.92 × EELVCT + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI95%: 4-10%]. EELVMBNW adequately tracked EELVCT changes over time (concordance rate amounting to 100% [CI95%: 87%-100%] and angular bias amounting to - 2° ± 10°). VrecMBNW and VrecCT were significantly correlated (R2 = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased. CONCLUSIONS: We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability.

Combined use of a broad-panel respiratory multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP): a multicentre, parallel-group, open-label, individual randomised trial conducted in French intensive care units.

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.

Reliability and limits of transport-ventilators to safely ventilate severe patients in special surge situations.

BACKGROUND: Intensive Care Units (ICU) have sometimes been overwhelmed by the surge of COVID-19 patients. Extending ICU capacity can be limited by the lack of air and oxygen pressure sources available. Transport ventilators requiring only one O2 source may be used in such places. OBJECTIVE: To evaluate the performances of four transport ventilators and an ICU ventilator in simulated severe respiratory conditions. MATERIALS AND METHODS: Two pneumatic transport ventilators, (Oxylog 3000, Draeger; Osiris 3, Air Liquide Medical Systems), two turbine transport ventilators (Elisee 350, ResMed; Monnal T60, Air Liquide Medical Systems) and an ICU ventilator (Engström Carestation-GE Healthcare) were evaluated on a Michigan test lung. We tested each ventilator with different set volumes (Vtset = 350, 450, 550 ml) and compliances (20 or 50 ml/cmH2O) and a resistance of 15 cmH2O/l/s based on values described in COVID-19 Acute Respiratory Distress Syndrome. Volume error (percentage of Vtset) with P0.1 of 4 cmH2O and trigger delay during assist-control ventilation simulating spontaneous breathing activity with P0.1 of 4 cmH2O and 8 cmH2O were measured. RESULTS: Grouping all conditions, the volume error was 2.9 ± 2.2% for Engström Carestation; 3.6 ± 3.9% for Osiris 3; 2.5 ± 2.1% for Oxylog 3000; 5.4 ± 2.7% for Monnal T60 and 8.8 ± 4.8% for Elisee 350. Grouping all conditions (P0.1 of 4 cmH2O and 8 cmH2O), trigger delay was 50 ± 11 ms, 71 ± 8 ms, 132 ± 22 ms, 60 ± 12 and 67 ± 6 ms for Engström Carestation, Osiris 3, Oxylog 3000, Monnal T60 and Elisee 350, respectively. CONCLUSIONS: In surge situations such as COVID-19 pandemic, transport ventilators may be used to accurately control delivered volumes in locations, where only oxygen pressure supply is available. Performances regarding triggering function are acceptable for three out of the four transport ventilators tested.

Quantitative-analysis of computed tomography in COVID-19 and non COVID-19 ARDS patients: A case-control study.

PURPOSE: The aim of this study was to assess whether the computed tomography (CT) features of COVID-19 (COVID+) ARDS differ from those of non-COVID-19 (COVID-) ARDS patients. MATERIALS AND METHODS: The study is a single-center prospective observational study performed on adults with ARDS onset ≤72 h and a PaO2/FiO2 ≤ 200 mmHg. CT scans were acquired at PEEP set using a PEEP-FiO2 table with VT adjusted to 6 ml/kg predicted body weight. RESULTS: 22 patients were included, of whom 13 presented with COVID-19 ARDS. Lung weight was significantly higher in COVID- patients, but all COVID+ patients presented supranormal lung weight values. Noninflated lung tissue was significantly higher in COVID- patients (36 ± 14% vs. 26 ± 15% of total lung weight at end-expiration, p < 0.01). Tidal recruitment was significantly higher in COVID- patients (20 ± 12 vs. 9 ± 11% of VT, p < 0.05). Lung density histograms of 5 COVID+ patients with high elastance (type H) were similar to those of COVID- patients, while those of the 8 COVID+ patients with normal elastance (type L) displayed higher aerated lung fraction.

Voxel-wise assessment of lung aeration changes on CT images using image registration: application to acute respiratory distress syndrome (ARDS).

PURPOSE: (1) To improve the accuracy of global and regional alveolar-recruitment quantification in CT scan pairs by accounting for lung-tissue displacements and deformation, (2) To propose a method for local-recruitment calculation. METHODS: Recruitment was calculated by subtracting the quantity of non-aerated lung tissues between expiration and inspiration. To assess global recruitment, lung boundaries were first interactively delineated at inspiration, and then they were warped based on automatic image registration to define the boundaries at expiration. To calculate regional recruitment, the lung mask defined at inspiration was cut into pieces, and these were also warped to encompass the same tissues at expiration. Local-recruitment map was calculated as follows: For each voxel at expiration, the matching location at inspiration was determined by image registration, non-aerated voxels were counted in the neighborhood of the respective locations, and the voxel count difference was normalized by the neighborhood size. The methods were evaluated on 120 image pairs of 12 pigs with experimental acute respiratory distress syndrome. RESULTS: The dispersion of global- and regional-recruitment values decreased when using image registration, compared to the conventional approach neglecting tissue motion. Local-recruitment maps overlaid onto the original images were visually consistent, and the sum of these values over the whole lungs was very close to the global-recruitment estimate, except four outliers. CONCLUSIONS: Image registration can compensate lung-tissue displacements and deformation, thus improving the quantification of alveolar recruitment. Local-recruitment calculation can also benefit from image registration, and its values can be overlaid onto the original image to display a local-recruitment map. They also can be integrated over arbitrarily shaped regions to assess regional or global recruitment.

Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation.

BACKGROUND: Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. METHODS: This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. RESULTS: There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80-1.00) and 0.65 (95% CI, 0.46-0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67-100), and specificity of 89% (95% CI, 72-100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24-0.80) and 0.59 (95% CI, 0.31-0.88), respectively. CONCLUSIONS: Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient.

Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort.

BACKGROUND: In pressure-controlled (PC) ventilation, tidal volume (V T) and transpulmonary pressure (P L ) result from the addition of ventilator pressure and the patient's inspiratory effort. PC modes can be classified into fully, partially, and non-synchronized modes, and the degree of synchronization may result in different V T and P L despite identical ventilator settings. This study assessed the effects of three PC modes on V T, P L , inspiratory effort (esophageal pressure-time product, PTPes), and airway occlusion pressure, P 0.1. We also assessed whether P 0.1 can be used for evaluating patient effort. METHODS: Prospective, randomized, crossover physiologic study performed in 14 spontaneously breathing mechanically ventilated patients recovering from acute respiratory failure (1 subsequently withdrew). PC modes were fully (PC-CMV), partially (PC-SIMV), and non-synchronized (PC-IMV using airway pressure release ventilation) and were applied randomly; driving pressure, inspiratory time, and set respiratory rate being similar for all modes. Airway, esophageal pressure, P 0.1, airflow, gas exchange, and hemodynamics were recorded. RESULTS: V T was significantly lower during PC-IMV as compared with PC-SIMV and PC-CMV (387 ± 105 vs 458 ± 134 vs 482 ± 108 mL, respectively; p < 0.05). Maximal P L was also significantly lower (13.3 ± 4.9 vs 15.3 ± 5.7 vs 15.5 ± 5.2 cmH2O, respectively; p < 0.05), but PTPes was significantly higher in PC-IMV (215.6 ± 154.3 vs 150.0 ± 102.4 vs 130.9 ± 101.8 cmH2O × s × min-1, respectively; p < 0.05), with no differences in gas exchange and hemodynamic variables. PTPes increased by more than 15% in 10 patients and by more than 50% in 5 patients. An increased P 0.1 could identify high levels of PTPes. CONCLUSIONS: Non-synchronized PC mode lowers V T and P L in comparison with more synchronized modes in spontaneously breathing patients but can increase patient effort and may need specific adjustments. Clinical Trial Registration Clinicaltrial.gov # NCT02071277.

Can proportional ventilation modes facilitate exercise in critically ill patients? A physiological cross-over study : Pressure support versus proportional ventilation during lower limb exercise in ventilated critically ill patients.

BACKGROUND: Early exercise of critically ill patients may have beneficial effects on muscle strength, mass and systemic inflammation. During pressure support ventilation (PSV), a mismatch between demand and assist could increase work of breathing and limit exercise. A better exercise tolerance is possible with a proportional mode of ventilation (Proportional Assist Ventilation, PAV+ and Neurally Adjusted Ventilatory Assist, NAVA). We examined whether, in critically ill patients, PSV and proportional ventilation have different effects on respiratory muscles unloading and work efficiency during exercise. METHODS: Prospective pilot randomized cross-over study performed in a medico-surgical ICU. Patients requiring mechanical ventilation >48 h were enrolled. At initiation, the patients underwent an incremental workload test on a cycloergometer to determine the maximum level capacity. The next day, 2 15-min exercise, at 60% of the maximum capacity, were performed while patients were randomly ventilated with PSV and PAV+ or NAVA. The change in oxygen consumption (ΔVO2, indirect calorimetry) and the work efficiency (ratio of ΔVO2 per mean power) were computed. RESULTS: Ten patients were examined, 6 ventilated with PSV/PAV+ and 4 with PSV/NAVA. Despite the same mean inspiratory pressure at baseline between the modes, baseline VO2 (median, IQR) was higher during proportional ventilation (301 ml/min, 270-342) compared to PSV (249 ml/min, 206-353). Exercise with PSV was associated with a significant increase in VO2 (ΔVO2, median, IQR) (77.6 ml/min, 59.9-96.5), while VO2 did not significantly change during exercise with proportional modes (46.3 ml/min, 5.7-63.7, p < 0.05). As a result, exercise with proportional modes was associated with a better work efficiency than with PSV. The ventilator modes did not affect patient's dyspnea, limb fatigue, distance, hemodynamics and breathing pattern. CONCLUSIONS: Proportional ventilation during exercise results in higher work efficiency and less increase in VO2 compared to ventilation with PSV. These preliminary findings suggest that proportional ventilation could enhance the training effect and facilitate rehabilitation.

Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations from an expert panel from the French Intensive Care Society (SRLF) with the French Group for Pediatric Intensive Care Emergencies (GFRUP), the French Society of Anesthesia and Intensive Care (SFAR), the French Society of Hematology (SFH), the French Society for Hospital Hygiene (SF2H), and the French Infectious Diseases Society (SPILF).

Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society. Literature review and formulation of recommendations were performed using the Grading of Recommendations Assessment, Development and Evaluation system. Each recommendation was then evaluated and rated by each expert using a methodology derived from the RAND/UCLA Appropriateness Method. Six fields are covered by the provided recommendations: (1) ICU admission and prognosis, (2) protective isolation and prophylaxis, (3) management of acute respiratory failure, (4) organ failure and organ support, (5) antibiotic management and source control, and (6) hematological management. Most of the provided recommendations are obtained from low levels of evidence, however, suggesting a need for additional studies. Seven recommendations were, however, associated with high level of evidences and are related to protective isolation, diagnostic workup of acute respiratory failure, medical management, and timing surgery in patients with typhlitis.

Factors Associated With Treatment Failure of Infected Pressure Sores.

OBJECTIVE: In this study, we assess interdisciplinary surgical and medical parameters associated to recurrences of infected pressure ulcers. BACKGROUND: There is a little in the published literature regarding factors associated with the outcome of treatment of infected pressure ulcers. METHODS: We undertook a single-center review of spinal injured adults hospitalized for an infected pressure ulcer or implant-free osteomyelitis and reviewed the literature on this topic from 1990-2015. RESULTS: We found 70 lesions in 31 patients (52 with osteomyelitis) who had a median follow-up of 2.7 years (range, 4 months to 19 years). The median duration of antibiotic therapy was 6 weeks, of which 1 week was parenteral. Clinical recurrence after treatment was noted in 44 infected ulcers (63%), after a median interval of 1 year. In 86% of these recurrences, cultures yielded a different organism than the preceding episode. By multivariate analyses, the following factors were not significantly related to recurrence: number of surgical interventions (hazard ratio 0.9, 95% confidence interval 0.5-1.5); osteomyelitis (hazard ratio 1.5; 0.7-3.1); immune suppression; prior sacral infections, and duration of total (or just parenteral) antibiotic sue. Patients with antibiotic treatment for <6 weeks had the same failure rate as those with as >12 weeks (χ test; P = 0.90). CONCLUSIONS: In patients with infected pressure ulcers, clinical recurrence occurs in almost two-thirds of lesions, but in only 14% with the same pathogen(s). The number of surgical debridements, flap use, or duration of antibiotic therapy was not associated with recurrence, suggesting recurrences are caused by reinfections caused by other extrahospital factors.