Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial.

PURPOSE: Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care. METHODS: In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UFNET ≥ 100 ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25 ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population. RESULTS: Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms. CONCLUSION: In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.

INTRODUCTION: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. METHODS: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. RESULTS: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? CONCLUSION: These recommendations should optimize the use of oxygen during ARF.

SARS-CoV2 pneumonia patients admitted to the ICU: Analysis according to clinical and biological parameters and the extent of lung parenchymal lesions on chest CT scan, a monocentric observational study.

BACKGROUND: CT-scan and inflammatory and coagulation biomarkers could help in prognostication of COVID-19 in patients on ICU admission. OBJECTIVE: The objectives of this study were to measure the prognostic value of the extent of lung parenchymal lesions on computed tomography (CT) and of several coagulation and inflammatory biomarkers, and to explore the characteristics of the patients depending on the extent of lung parenchymal lesions. DESIGN: Retrospective monocentric observational study achieved on a dataset collected prospectively. SETTING: Medical ICU of the university hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged ≥18 years admitted between 20 March, 2020 and 31 August, 2021 for COVID-19 pneumonia. INTERVENTIONS: Characteristics at baseline and during ICU stay, and outcomes at day 60 were recorded. The extent of lung parenchyma lesions observed on the chest CT performed on admission was established by artificial intelligence software. MEASUREMENTS: Several clinical characteristics and laboratory features were collected on admission including plasma interleukin-6, HLA-DR monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day-60 mortality were investigated by uni- and multivariate survival analyses. RESULTS: 270 patients were included. Inflammation biomarkers including the levels of neutrophils, CRP, ferritin and Il10 were the indices the most associated with the severity of the extent of the lung lesions. Patients with more extensive lung parenchymal lesions (≥ 75%) on admission had higher CRP serum levels. The extent of lung parenchymal lesions was associated with a decrease in the PaO2/FiO2 ratio(p<0.01), fewer ventilatory-free days (p = 0.03), and a higher death rate at day 60(p = 0.01). Extent of the lesion of more than 75% was independently associated with day-60 mortality (aHR = 1.72[1.06; 2.78], p = 0.03). The prediction of death at day 60 was improved when considering simultaneously biological and radiological markers obtained on ICU admission (AUC = 0.78). CONCLUSIONS: The extent of lung parenchyma lesions on CT was associated with inflammation, and the combination of coagulation and inflammatory biomarkers and the extent of the lesions predicted the poorest outcomes.

Organisation of clinical research in intensive care units: A scoping review.

BACKGROUND: Clinical research is essential for the development and progress of therapies and procedures. Intensive care units (ICUs) manage the sickest patients. Numerous clinical trials are organised in ICUs to evaluate new treatments or support techniques. Concomitantly, new professions involved in clinical research set-ups are emerging. AIM: The aim of this scoping review was to identify the nature and extent of research evidence on the organisation of clinical research in ICUs. METHODS: This review focusses on observational and qualitative narrative studies dealing with clinical research organisation in ICUs, with a special interest in structures coordinating research, the roles of clinical research professionals, and the training required. Medline and Embase were analysed between January 2000 and June 2024. Assessment of the study quality was based on the Let Evidence Guide Every New Decision evaluation system and the Newcastle-Ottawa quality assessment scale. RESULTS: Of the 14 studies reviewed, four were narrative and 10 observational descriptive. All were based on cross-sectional surveys. Most studies were carried out in North America, the United Kingdom, and Australia/New Zealand. ICU clinical research professionals were mostly female nurses aged between 31 and 50 years who had a wide diversity of training profiles and performed greatly varied tasks from data collection to publication of the article. Reported job satisfaction depended on the degree of autonomy, the workload, the extent of professional recognition, and opportunities for professional promotion. CONCLUSIONS: The organisation of ICU clinical research reflects considerable diversity in training, tasks, job organisation, and responsibilities.

Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study.

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

Nutrition support, carbohydrate feeding and insulin sensitivity in the critically ill patient: a complex relationship.

PURPOSE OF REVIEW: This review aims to summarize recent studies that highlight the complex relationship between nutrition, carbohydrate, insulin provision and glycaemic control in the critically ill patient population. RECENT FINDINGS: Results of observational studies concur to support early hypoglycaemia and persisting hyperglycaemia as life-threatening events. In contrast, interventional studies indicate that early macronutrient restriction appears to reduce the benefits related to insulin therapy. This restriction is however associated with improved outcomes in itself. The potential role of modified enteral solutions as an adjunctive treatment to attenuate hyperglycaemia warrants further research. The selection of a therapeutic modality may also differ according to the characteristics of the setting, such as the nurse-to-patient ratio, the type and accuracy of meters, including near-continuous glucose monitoring and the availability of computer-guided protocols. SUMMARY: There appears to be significant interplay between nutrition, including carbohydrate provision, blood glucose control and clinical outcomes. Individualized care is probably needed to define the optimal glucose target and nutritional intervention. This can differ according to the preexistence of chronic hyperglycaemia, the timing from the onset of critical illness and the clinical condition itself.

Job description and perception of clinical research personnel working in a network of French intensive care units.

BACKGROUND: There is a lack of information about the organisation and management of clinical research personnel in Europe and of their professional activity in intensive care. We therefore conducted a cross-sectional survey among personnel currently working in a French intensive care research network that involves 41 centres nationwide. The aim of the survey was to describe the personnel's personal and institutional organisation and management, their job perception in terms of satisfaction and stress, and suggestions for improvement. METHODS: Over 3 months in 2023, the research personnel received an electronic questionnaire on their personal and professional profile, past and present training, workplace and functions currently performed, personal knowledge about job skills required, job satisfaction and stress by as measured on a rating scale, and suggested ways of improvement. RESULTS: Ninety seven people replied to the questionnaire (a response rate of 71.3%), of whom 78 (57.3%) were sufficiently involved in intensive care to provide complete answers. This core sample had profiles in line with French recruitment policies and comprised mainly Bachelor/Master graduates, with nurses accounting for only 21.8%. The female to male ratio was 77:23%. Many responders declared to have a shared activity of technician (for investigation) and assistant (for quality control). More than 70% of the responders considered that most of the tasks required of each worker were major. Figures were much lower for project managers, who were few to take part in the survey. On a scale of 10, the median of job satisfaction was 7 for personal work organisation, 6 for training and for institutional organisation, and only 5 for personal career management. The median of job stress was 5 and was inversely correlated with satisfaction with career management. Respect of autonomy, work-sharing activity between investigation and quality control, a better career progression, financial reward for demanding tasks, and participation in unit staff meetings were the main suggestions to improve employee satisfaction. CONCLUSION: This nationwide survey provides a new insight into the activity of French clinical research personnel and points to ways to improve the quality and efficiency of this workforce.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.

KEY MESSAGES: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. BACKGROUND: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. METHODS: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock. RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. CONCLUSIONS: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.

Right ventricular injury in critically ill patients with COVID-19: a descriptive study with standardized echocardiographic follow-up.

PURPOSE: Patients with COVID-19 admitted to intensive care unit (ICU) may have right ventricular (RV) injury. The main goal of this study was to investigate the incidence of RV injury and to describe the patient trajectories in terms of RV injury during ICU stay. METHODS: Prospective and bicentric study with standardized transthoracic echocardiographic (TTE) follow-up during ICU stay with a maximum follow-up of 28 days. The different patterns of RV injury were isolated RV dilation, RV dysfunction (tricuspid annular plane systolic excursion < 17 mm and/or systolic tricuspid annular velocity < 9.5 cm/s and/or RV fractional area change < 35%) without RV dilation, RV dysfunction with RV dilation and acute cor pulmonale (ACP, RV dilatation with paradoxical septal motion). The different RV injury patterns were described and their association with Day-28 mortality was investigated. RESULTS: Of 118 patients with complete echocardiographic follow-up who underwent 393 TTE examinations during ICU stay, 73(62%) had at least one RV injury pattern during one or several TTE examinations: 29(40%) had isolated RV dilation, 39(53%) had RV dysfunction without RV dilation, 10(14%) had RV dysfunction with RV dilation and 2(3%) had ACP. Patients with RV injury were more likely to have cardiovascular risk factors, to be intubated and to receive norepinephrine and had a higher Day-28 mortality rate (27 vs. 7%, p < 0.01). RV injury was isolated in 82% of cases, combined with left ventricular systolic dysfunction in 18% of cases and 10% of patients with RV injury experienced several patterns of RV injury during ICU stay. The number of patients with de novo RV injury decreased over time, no patient developed de novo RV injury after Day-14 regardless of the RV injury pattern and 20(31%) patients without RV injury on ICU admission developed RV injury during ICU stay. Only the combination of RV dysfunction with RV dilation or ACP (aHR = 3.18 95% CI(1.16-8.74), p = 0.03) was associated with Day-28 mortality. CONCLUSION: RV injury was frequent in COVID-19 patients, occurred within the first two weeks after ICU admission and was most often isolated. Only the combination of RV dysfunction with RV dilation or ACP could potentially be associated with Day-28 mortality. Clinical trial registration NCT04335162.

Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database.

BACKGROUND: Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM. METHODS: We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, "Direct ICU" corresponding to a direct ICU admission and "Delayed ICU" corresponding to a secondary ICU admission. RESULTS: We identified 4052 patients hospitalized for a first episode of PM, including 2006 "Direct ICU" patients (50%) and 2046 "delayed ICU" patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50-71] and a median Charlson index of 1 [0-3]. Among them, median SAPS II on admission was 46 [33-62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2-14] and 21 days [13-38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56-0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU. CONCLUSIONS: Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission.

Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia in Critically Ill Patients: A Cluster Analysis According to Baseline Characteristics, Biological Features, and Chest CT Scan on Admission.

BACKGROUND: Inconsistent results from COVID-19 studies raise the issue of patient heterogeneity. OBJECTIVE: The objective of this study was to identify homogeneous subgroups of patients (clusters) using baseline characteristics including inflammatory biomarkers and the extent of lung parenchymal lesions on CT, and to compare their outcomes. DESIGN: Retrospective single-center study. SETTING: Medical ICU of the University Hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged greater than or equal to 18 years, admitted between March 20, 2020, and August 31, 2021, for COVID-19 pneumonia. INTERVENTIONS: Characteristics at baseline, during ICU stay, and outcomes at day 60 were recorded. On the chest CT performed at admission the extent of lung parenchyma lesions was established by artificial intelligence software. MEASUREMENTS AND MAIN RESULTS: Clusters were determined by hierarchical clustering on principal components using principal component analysis of admission characteristics including plasma interleukin-6, human histocompatibility leukocyte antigen-DR expression rate on blood monocytes (HLA-DR) monocytic-expression rate (mHLA-DR), and the extent of lung parenchymal lesions. Factors associated with day 60 mortality were investigated by univariate survival analysis. Two hundred seventy patients were included. Four clusters were identified and three were fully described. Cluster 1 (obese patients, with moderate hypoxemia, moderate extent of lung parenchymal lesions, no inflammation, and no down-regulation of mHLA-DR) had a better prognosis at day 60 (hazard ratio [HR] = 0.27 [0.15-0.46], p < 0.01), whereas cluster 2 (older patients with comorbidities, moderate extent of lung parenchyma lesions but significant hypoxemia, inflammation, and down-regulation of mHLA-DR) and cluster 3 (patients with severe parenchymal disease, hypoxemia, inflammatory reaction, and down-regulation of mHLA-DR) had an increased risk of mortality (HR = 2.07 [1.37-3.13], p < 0.01 and HR = 1.52 [1-2.32], p = 0.05, respectively). In multivariate analysis, only clusters 1 and 2 were independently associated with day 60 death. CONCLUSIONS: Three clusters with distinct characteristics and outcomes were identified. Such clusters could facilitate the identification of targeted populations for the next trials.

Mortality, incidence, and microbiological documentation of ventilated acquired pneumonia (VAP) in critically ill patients with COVID-19 or influenza.

BACKGROUND: Data on ventilator associated pneumonia (VAP) in COVID-19 and influenza patients admitted to intensive care units (ICU) are scarce. This study aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for at least 48 h, either for COVID-19 or for influenza, and to describe the epidemiological characteristics in each group of VAP. DESIGN: Multicentre retrospective observational study. SETTING: Eleven ICUs of the French OutcomeRea™ network. PATIENTS: Patients treated with invasive mechanical ventilation (IMV) for at least 48 h for either COVID-19 or for flu. RESULTS: Of the 585 patients included, 503 had COVID-19 and 82 had influenza between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the COVID-19 and flu patients, VAP incidences for the first VAP episode were, respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01), respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36; 2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza (aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33], p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33], p = 0.35). CONCLUSION: The incidence of VAP was higher in patients ventilated for at least 48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were the most frequently detected microorganisms. In patients ventilated for either COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of mortality.

Body composition and muscle strength at the end of ICU stay are associated with 1-year mortality, a prospective multicenter observational study.

BACKGROUND & AIMS: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay. METHODS: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality. RESULTS: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%. CONCLUSION: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied.

Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with acute exacerbation of COPD: From the French OUTCOMEREA cohort.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial.

BACKGROUND: The respective benefits of high and low doses of dexamethasone (DXM) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and acute respiratory failure (ARF) are controversial, with two large triple-blind RCTs reaching very important difference in the effect-size. In the COVIDICUS trial, no evidence of additional benefit of high-dose dexamethasone (DXM20) was found. We aimed to explore whether some specific patient phenotypes could benefit from DXM20 compared to the standard of care 6 mg dose of DXM (DXMSoC). METHODS: We performed a post hoc exploratory Bayesian analysis of 473 patients who received either DXMSoc or DXM20 in the COVIDICUS trial. The outcome was the 60 day mortality rate of DXM20 over DXMSoC, with treatment effect measured on the hazard ratio (HR) estimated from Cox model. Bayesian analyses allowed to compute the posterior probability of a more than trivial benefit (HR < 0.95), and that of a potential harm (HR > 1.05). Bayesian measures of interaction then quantified the probability of interaction (Pr Interact) that the HR of death differed across the subsets by 20%. Primary analyses used noninformative priors, centred on HR = 1.00. Sensitivity analyses used sceptical and enthusiastic priors, based on null (HR = 1.00) or benefit (HR = 0.95) effects. RESULTS: Overall, the posterior probability of a more than trivial benefit and potential harm was 29.0 and 51.1%, respectively. There was some evidence of treatment by subset interaction (i) according to age (Pr Interact, 84%), with a 86.5% probability of benefit in patients aged below 70 compared to 22% in those aged above 70; (ii) according to the time since symptoms onset (Pr Interact, 99%), with a 99.9% probability of a more than trivial benefit when lower than 7 days compared to a < 0.1% probability when delayed by 7 days or more; and (iii) according to use of remdesivir (Pr Interact, 91%), with a 90.1% probability of benefit in patients receiving remdesivir compared to 19.1% in those who did not. CONCLUSIONS: In this exploratory post hoc Bayesian analysis, compared with standard-of-care DXM, high-dose DXM may benefit patients aged less than 70 years with severe ARF that occurred less than 7 days after symptoms onset. The use of remdesivir may also favour the benefit of DXM20. Further analysis is needed to confirm these findings. TRIAL REGISTRATION: NCT04344730, date of registration April 14, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04344730?term=NCT04344730&draw=2&rank=1 ); EudraCT: 2020-001457-43 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-001457-43 ).

Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial.

BACKGROUND: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS. METHODS: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618. FINDINGS: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004). INTERPRETATION: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS. FUNDING: French Ministry of Solidarity and Health and Hospices Civils de Lyon.

Epidemiology and Outcome of Early-Onset Acute Kidney Injury and Recovery in Critically Ill COVID-19 Patients: A Retrospective Analysis.

BACKGROUND: The clinical significance of early-onset acute kidney injury (EO-AKI) and recovery in severe COVID-19 intensive care unit (ICU) patients is poorly documented. OBJECTIVE: The aim of the study was to assess the epidemiology and outcome of EO-AKI and recovery in ICU patients admitted for SARS-CoV-2 pneumonia. DESIGN: This was a retrospective single-centre study. SETTING: The study was carried out at the medical ICU of the university hospital of Clermont-Ferrand, France. PATIENTS: All consecutive adult patients aged ≥18 years admitted between 20 March 2020 and 31 August 2021 for SARS-CoV-2 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and with an ICU length of stay (LOS) ≤72 h were excluded. INTERVENTIONS: EO-AKI was defined on the basis of serum creatinine levels according to the Kidney Disease Improving Global Outcomes criteria, developing ≤7 days. Depending on renal recovery, defined by the normalization of serum creatinine levels, EO-AKI was transient (recovery within 48 h), persistent (recovery between 3 and 7 days) or AKD (no recovery within 7 days after EO-AKI onset). MEASUREMENTS: Uni- and multivariate analyses were performed to determine factors associated with EO-AKI and EO-AKI recovery. MAIN RESULTS: EO-AKI occurred in 84/266 (31.5%) study patients, of whom 42 (50%), 17 (20.2%) and 25 (29.7%) had EO-AKI stages 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 40 (47.6%), 15 (17.8%) and 29 (34.6%) patients, respectively. The 90-day mortality was 87/244 (35.6%) and increased with EO-AKI occurrence and severity: no EO-AKI, 38/168 (22.6%); EO-AKI stage 1, 22/39 (56.4%); stage 2, 9/15 (60%); and stage 3, 18/22 (81.8%) (p < 0.01). The 90-day mortality in patients with transient or persistent AKI and AKD was 20/36 (55.6%), 8/14 (57.1%) and 21/26 (80.8%), respectively (p < 0.01). MAKE-90 occurred in 42.6% of all patients. CONCLUSIONS: In ICU patients admitted for SARS-CoV-2 pneumonia, the development of EO-AKI and time to recovery beyond day 7 of onset were associated with poor outcome.