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Abstract Background Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. Mortality rate remains high but improvement has been described over the past several years. We aimed to describe characteristics and outcomes of ARDS in HM patients admitted in French ICUs (Intensive Care Units) during a one year-period. Data for this nationwide cohort study were collected from the French national hospital database (Programme de Médicalisation des Systèmes d’Information (PMSI)). All patients (18 years or older) admitted to French ICUs in 2017 and with a diagnosis of ARDS were included. Three groups were compared according to the presence of an HM, a solid cancer or no cancer. The primary endpoint was 90-day mortality. Secondary endpoints were the description of ICU management, etiologies of ARDS and mortality risk factors. Results A total of 12 846 patients with ARDS were included. Among them, 990 had HM and 2744 had a solid cancer. The main malignancies were non-Hodgkin lymphoma (NHL) (28.5%), acute myeloid leukemia (AML) (20.4%) and multiple myeloma (19.7%). Day-90 mortality in patients with HM was higher than in patients with no cancer (64.4% vs. 46.6% p = 0.01) but was not different from that of patients with solid cancer (64.4% vs. 61.4%,p = 0.09). Intubation rate was lower in patients with HM in comparison with both groups (87.7% vs. 90.4% p = 0.02 for patients with solid cancer and 87.7% vs. 91.3%; p

Abstract 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.

Abstract Background Before the Coronavirus Disease 2019 (COVID-19) pandemic in France, undocumented migrants had a higher risk than general population for being admitted to the intensive care unit (ICU) because of acute respiratory failure or severe infection. Specific data concerning the impact of COVID-19 on undocumented migrants in France are lacking. We aimed to analyze the mortality and respiratory severity of COVID-19 in this specific population. We retrospectively included all undocumented adult migrants admitted in French ICUs from March 2020 through April 2021 using the French nationwide hospital information system (Programme de Médicalisation des Systèmes d’Information). We focused on admissions related to COVID-19. Undocumented migrants were compared to the general population, first in crude analysis, then after matching on age, severity and main comorbidities. The primary outcome was the ICU mortality from COVID-19. Secondary objectives were the incidence of acute respiratory distress syndrome (ARDS), the need for mechanical ventilation (MV), the duration of MV, ICU and hospital stay. Results During the study period, the rate of ICU admission among patients hospitalized for COVID-19 was higher for undocumented migrants than for general population (463/1627 (28.5%) vs. 81 813/344 001 (23.8%); p

Abstract Background Healthcare-associated infections involving Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) phenotype are associated with impaired patient-centered outcomes and poses daily therapeutic challenges in most of intensive care units worldwide. Over the recent years, four innovative β-lactam/β-lactamase inhibitor (BL/BLI) combinations (ceftolozane–tazobactam, ceftazidime–avibactam, imipenem–relebactam and meropenem–vaborbactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of certain DTR-GNB infections. The literature addressing their microbiological spectrum, pharmacokinetics, clinical efficacy and safety was exhaustively audited by our group to support the recent guidelines of the French Intensive Care Society on their utilization in critically ill patients. This narrative review summarizes the available evidence and unanswered questions on these issues. Methods A systematic search for English-language publications in PUBMED and the Cochrane Library database from inception to November 15, 2022. Results These drugs have demonstrated relevant clinical success rates and a reduced renal risk in most of severe infections for whom polymyxin- and/or aminoglycoside-based regimen were historically used as last-resort strategies—namely, ceftazidime–avibactam for infections due to Klebsiella pneumoniae carbapenemase (KPC)- or OXA-48-like-producing Enterobacterales, meropenem–vaborbactam for KPC-producing Enterobacterales, ceftazidime–avibactam/aztreonam combination or cefiderocol for metallo-β-lactamase (MBL)-producing Enterobacterales, and ceftolozane–tazobactam, ceftazidime–avibactam and imipenem–relebactam for non-MBL-producing DTR Pseudomonas aeruginosa. However, limited clinical evidence exists in critically ill patients. Extended-infusion scheme (except for imipenem–relebactam) may be indicated for DTR-GNB with high minimal inhibitory concentrations and/or in case of augmented renal clearance. The potential benefit of combining these agents with other antimicrobials remains under-investigated, notably for the most severe presentations. Other important knowledge gaps include pharmacokinetic information in particular situations (e.g., pneumonia, other deep-seated infections, and renal replacement therapy), the hazard of treatment-emergent resistance and possible preventive measures, the safety of high-dose regimen, the potential usefulness of rapid molecular diagnostic tools to rationalize their empirical utilization, and optimal treatment durations. Comparative clinical, ecological, and medico-economic data are needed for infections in whom two or more of these agents exhibit in vitro activity against the causative pathogen. Conclusions New BL/BLI combinations and cefiderocol represent long-awaited options for improving the management of DTR-GNB infections. Several research axes must be explored to better define the positioning and appropriate administration scheme of these drugs in critically ill patients.

Abstract Background Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. Methods We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. Results Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality. Conclusions SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Abstract Background Since March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival. Results Between March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3–10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62–81), median PaCO2 of 58 mmHg (IQR 51–66) and a median arterial pH of 7.33 (IQR 7.25–7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644–0.934), p = 0.007) and 0.631 (0.462–0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004–1.285), p = 0.044 and 1.187 (1.035–1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance. Conclusion In this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.

Abstract Background Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. Results Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups. Conclusions In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.

Abstract Background The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. Methods This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). Results The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups. Conclusions In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Abstract Background Data on respiratory mechanics of COVID-19 ARDS patients are scarce. Respiratory mechanics and response to positive expiratory pressure (PEEP) may be different in obese and non-obese patients. Methods We investigated esophageal pressure allowing determination of transpulmonary pressures (PL ) and elastances (EL) during a decremental PEEP trial from 20 to 6 cm H2O in a cohort of COVID-19 ARDS patients. Results Fifteen patients were investigated, 8 obese and 7 non-obese patients. PEEP ≥ 16 cm H2O for obese patients and PEEP ≥10 cm H2O for non-obese patients were necessary to obtain positive expiratory P L . Change of PEEP did not alter significantly ΔP L or elastances in obese patients. However, in non-obese patients lung EL and ΔP L increased significantly with PEEP increase. Chest wall EL was not affected by PEEP variations in both groups.

Abstract Background Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). Methods Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”. Results We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59). Conclusion In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT

Abstract Background Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS). However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO). We tried to determine the frequency of Herpesviridae reactivation and its impact on patients’ prognosis during ECMO for severe ARDS. Results During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a veno-venous ECMO were included. Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone). HSV reactivation occurred earlier than CMV after the beginning of MV [(6–15) vs. 19 (13–29) days; p

Abstract Background Lung fibroproliferation in ARDS patients is associated with mortality. Alveolar procollagen III (NT-PCP-III) is a validated biomarker of lung fibroproliferation. A chest CT scan could be useful for the diagnosis of lung fibroproliferation. The aim of this study was to identify lung fibroproliferative CT scan aspects in ARDS patients with high levels of NT-PCP-III. Results This retrospective study included ARDS patients who had at least one assessment of alveolar NT-PCP-III and a chest CT scan within 3 days before or after NT-PCP-III determination. An alveolar level of NT-PCP-III > 9 µG/L indicated fibroproliferation. The CT scan was scored on interstitial and alveolar abnormalities. Each lobe was scored from 0 to 5 according to the severity of the abnormalities. The crude score and the corrected score (related to the number of scored lobes in cases of important lobar condensation or lobectomy) were used. One hundred ninety-two patients were included, for a total of 228 alveolar NT-PCP-III level and CT scan ‘couples’. Crude and corrected CT scan fibrosis scores were higher in the fibroproliferation group compared with the no fibroproliferation group (crude score: 12 [9–17] vs 14 [11–12], p = 0.002; corrected score: 2.8 [2.2–4.0] vs 3.4 [2.5–4.7], p

Abstract Background The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. Results The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Conclusions HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Abstract Background Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices. This study aims to evaluate the rate of both colonisations and infections related to ECMO devices at the time of ECMO removal. Results We included all consecutive adult patients treated with venovenous ECMO (VV-ECMO) for at least 48 h during a 34-month study. At the time of ECMO removal, blood cultures, swab cultures on insertion cannula site and intravascular cannula extremity cultures were systematically performed. Each ECMO device was classified according to the infectious status into three groups: (1) uninfected/uncolonised ECMO device, (2) ECMO device colonisation and (3) ECMO device infection. Ninety-nine patients underwent 103 VV-ECMO, representing 1472 ECMO days. The ECMO device infection rate was 9.7% (10 events), including 7 ECMO device-related bloodstream infections (6.8%). The ECMO device colonisation rate was 32% (33 events). No difference was observed between the three groups, regarding days of mechanical ventilation, ICU length of stay, ICU mortality and in-hospital mortality. We observed a longer ECMO duration in the ECMO device colonisation group as compared to the uninfected/uncolonised ECMO device group [12 (9–20 days) vs. 5 days (5–16 days), respectively, p

Abstract Background Neuromuscular blocking agents (NMBAs) have been shown to improve the outcome of the most severely hypoxemic, acute respiratory distress syndrome (ARDS) patients. However, the recommended dosage as well as the necessity of monitoring the neuromuscular block is unknown. We aimed to evaluate the efficiency of a nurse-directed protocol of NMBA administration based on a train-of-four (TOF) assessment to ensure a profound neuromuscular block and decrease cisatracurium consumption compared to an elevated and constant dose regimen. A prospective open labeled study was conducted in two medical intensive care units of two French university hospitals. Consecutive ARDS patients with a PaO2/FiO2 ratio less than 120 with a PEEP ≥5 cm H2O were included. Cisatracurium administration was driven by the nurses according to an algorithm based on TOF monitoring. The primary endpoint was cisatracurium consumption. The secondary endpoints included the quality of the neuromuscular block, the occurrence of adverse events, and the evolution of ventilatory and blood gas parameters. Results Thirty patients were included. NMBAs were used for 54 ± 30 h. According to this new algorithm, the initial dosage of cisatracurium was 11.8 ± 2 mg/h, and the final dosage was 14 ± 4 mg/h, which was significantly lower than in the ACURASYS study protocol (37.5 mg/h with a constant infusion rate (p