Inadequate intensive care physician supply in France: a point-prevalence prospective study.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities. RESULTS: Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements. CONCLUSION: The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.

Thrombolysis before venoarterial ECMO for high-risk pulmonary embolism: a retrospective cohort study.

PURPOSE: Despite systemic thrombolysis, a few patients with high-risk pulmonary embolism (PE) remain hemodynamically unstable. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a considerable lifesaving therapy but systemic thrombolysis before cannulation could carry a high risk of hemorrhage and alter the prognosis. METHODS: Between June 2012 and June 2023, we retrospectively analyzed from three intensive care units in Sorbonne University, ECMO-related complications and 90-day mortality for high-risk PE patients who received ECMO without previous systemic thrombolysis compared to those cannulated after systemic thrombolysis failure. Hospital discharge survivors were assessed for long-term health-related quality of life and echocardiographic evaluations. RESULTS: 72 high-risk PE patients [median age 48 (37-61) years, Simplified Acute Physiology Score II (SAPS II) 74 (60-85)] were placed on VA-ECMO for 5 (5-7) days. 31 (43%) patients underwent pre-ECMO thrombolysis (thrombolysis ECMO group, T +) compared to 41 patients (57%, no thrombolysis ECMO group, T-). There was more pre-ECMO cardiac arrest in the thrombolysis ECMO group (94% vs. 67%, p = 0.02). Ninety-day survival was not different between groups (39% vs 46%, log-rank test, p = 0.31). There was no difference in severe hemorrhages (61% vs 59%, p = 1). Twenty-five over 28 patients attended follow-up at a median time of 69 (52-95) months. Long-term quality of life was acceptable and none of them experienced chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Ninety-day survival and bleeding events rates did not differ in patients treated with VA-ECMO after systemic thrombolysis compared to those who were not. Recent systemic thrombolysis, as a single parameter, should not be considered as a contraindication for VA-ECMO in high-risk PE.

Isoproterenol improves hemodynamics and right ventricle-pulmonary artery coupling after heart transplantation.

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m2 (P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg-1 (P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included. RESULTS: We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP. CONCLUSION: ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support.

OBJECTIVE: To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence. METHODS: Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence. RESULTS: Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7-13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5-7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8-10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short- and prolonged-antimicrobial treatment. CONCLUSIONS: In patients with severe Covid-19-ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.

Venoarterial extracorporeal membrane oxygenation in immunocompromised patients with cardiogenic shock: a cohort study and propensity-weighted analysis.

PURPOSE: The outcomes of immunocompromised patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are seldom documented, making ECMO candidacy decisions challenging. This study aims (1) to report outcomes of immunocompromised patients treated with VA-ECMO, (2) to identify pre-ECMO predictors of 90-day mortality, (3) to assess the impact of immunodepression on 90-day mortality, and (4) to describe the main ECMO-related complications. METHODS: This is a retrospective, propensity-weighted study conducted in two French experienced ECMO centers. RESULTS: From January 2006 to January 2022, 177 critically ill immunocompromised patients (median (interquartile range, IQR) age 49 (32-60) years) received VA-ECMO. The main causes of immunosuppression were long-term corticosteroids/immunosuppressant treatment (29%), hematological malignancy (26%), solid organ transplant (20%), and solid tumor (13%). Overall 90-day and 1-year mortality were 70% (95% confidence interval (CI) 63-77%) and 75% (95% CI 65-79%), respectively. Older age and higher pre-ECMO lactate were independently associated with 90-day mortality. Across immunodepression causes, 1-year mortality ranged from 58% for patients with infection by human immunodeficiency virus (HIV) or asplenia, to 89% for solid organ transplant recipients. Hemorrhagic and infectious complications affected 39% and 54% of patients, while more than half the stay in intensive care unit (ICU) was spent on antibiotics. In a propensity score-weighted model comparing the 177 patients with 942 non-immunocompromised patients experiencing cardiogenic shock on VA-ECMO, immunocompromised status was independently associated with a higher 90-day mortality (odds ratio 2.53, 95% CI 1.72-3.79). CONCLUSION: Immunocompromised patients undergoing VA-ECMO treatment face an unfavorable prognosis, with higher 90-day mortality compared to non-immunocompromised patients. This underscores the necessity for thorough evaluation and careful selection of ECMO candidates within this frail population.

Ceftazidime/avibactam serum concentration in patients on ECMO.

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing. METHODS: Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing. RESULTS: Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition. CONCLUSIONS: In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing.

Increasing Sweep Gas Flow Reduces Respiratory Drive and Dyspnea in Nonintubated Venoarterial Extracorporeal Membrane Oxygenation Patients: A Pilot Study.

BACKGROUND: Data on assessment and management of dyspnea in patients on venoarterial extracorporeal membrane oxygenation (ECMO) for cardiogenic shock are lacking. The hypothesis was that increasing sweep gas flow through the venoarterial extracorporeal membrane oxygenator may decrease dyspnea in nonintubated venoarterial ECMO patients exhibiting clinically significant dyspnea, with a parallel reduction in respiratory drive. METHODS: Nonintubated, spontaneously breathing, supine patients on venoarterial ECMO for cardiogenic shock who presented with a dyspnea visual analog scale (VAS) score of greater than or equal to 40/100 mm were included. Sweep gas flow was increased up to +6 l/min by three steps of +2 l/min each. Dyspnea was assessed with the dyspnea-VAS and the Multidimensional Dyspnea Profile. The respiratory drive was assessed by the electromyographic activity of the alae nasi and parasternal muscles. RESULTS: A total of 21 patients were included in the study. Upon inclusion, median dyspnea-VAS was 50 (interquartile range, 45 to 60) mm, and sweep gas flow was 1.0 l/min (0.5 to 2.0). An increase in sweep gas flow significantly decreased dyspnea-VAS (50 [45 to 60] at baseline vs. 20 [10 to 30] at 6 l/min; P < 0.001). The decrease in dyspnea was greater for the sensory component of dyspnea (-50% [-43 to -75]) than for the affective and emotional components (-17% [-0 to -25] and -12% [-0 to -17]; P < 0.001). An increase in sweep gas flow significantly decreased electromyographic activity of the alae nasi and parasternal muscles (-23% [-36 to -10] and -20 [-41 to -0]; P < 0.001). There was a significant correlation between the sweep gas flow and the dyspnea-VAS (r = -0.91; 95% CI, -0.94 to -0.87), between the respiratory drive and the sensory component of dyspnea (r = 0.29; 95% CI, 0.13 to 0.44) between the respiratory drive and the affective component of dyspnea (r = 0.29; 95% CI, 0.02 to 0.54) and between the sweep gas flow and the alae nasi and parasternal (r = -0.31; 95% CI, -0.44 to -0.22; and r = -0.25; 95% CI, -0.44 to -0.16). CONCLUSIONS: In critically ill patients with venoarterial ECMO, an increase in sweep gas flow through the oxygenation membrane decreases dyspnea, possibly mediated by a decrease in respiratory drive.

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Procalcitonin as a biomarker to guide treatments for patients with lower respiratory tract infections.

INTRODUCTION: Lower respiratory tract infections are amongst the main causes for hospital/intensive care unit admissions and antimicrobial prescriptions. In order to reduce antimicrobial pressure, antibiotic administration could be optimized through procalcitonin-based algorithms. AREAS COVERED: In this review, we discuss the performances of procalcitonin for the diagnosis and the management of community-acquired and ventilator-associated pneumonia. We provide up-to-date evidence and deliver clear messages regarding the purpose of procalcitonin to reduce unnecessary antimicrobial exposure. EXPERT OPINION: Antimicrobial pressure and resulting antimicrobial resistances are a major public health issue as well as a daily struggle in the management of patients with severe infectious diseases, especially in intensive care units where antibiotic exposure is high. Procalcitonin-guided antibiotic administration has proven its efficacy in reducing unnecessary antibiotic use in lower respiratory tract infections without excess in mortality, hospital length of stay or disease relapse. Procalcitonin-guided algorithms should be implemented in wards taking care of patients with severe infections. However, procalcitonin performances are different regarding the setting of the infection (community versus hospital-acquired infections) the antibiotic management (start or termination of antibiotic) as well as patient's condition (immunosuppressed or in shock) and we encourage the physicians to be aware of these limitations.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study.

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

Diagnostic yield, safety and therapeutic consequences of myocardial biopsy in clinically suspected fulminant myocarditis unweanable from mechanical circulatory support.

BACKGROUND: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). METHODS: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. RESULTS: Forty-seven patients (median age 41 [30-47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients. CONCLUSIONS: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS.

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Systemic lupus erythematosus-related acute lung disease.

INTRODUCTION: Systemic lupus erythematosus (SLE) is non-organ specific autoimmune disease with mainly skin, joint, and kidney involvement. SLE-related acute lung disease (ALD) is rare, poorly investigated and can lead to acute respiratory failure. We conducted a retrospective study aiming to describe clinical features, treatments and outcome of SLE-related APD. METHODS: We retrospectively included all patients with SLE and ALD admitted from November 1996 and September 2018 to La Pitié-Salpêtrière Hospital, after exclusion of viral or bacterial lung infection, cardiac failure or any other alternate diagnosis. RESULTS: During the time of the study, 14 patients with 16 episodes were admitted to our center: female 79%, mean age ± SD at admission 24 ± 11 years. ALD was inaugural of the SLE in 70% cases. SLE main organ involvement were: arthritis 93%, skin 79%, serositis 79%, hematological 79%, kidney 64%, neuropsychiatric 36% and cardiac 21%. 11 episodes required ICU admission for a median time of 8 days. Chest CT-scan revealed mostly basal consolidation and ground-glass opacities. When available, bronchoalveolar lavage mostly revealed a neutrophilic alveolitis with alveolar hemorrhage in 67% cases. Symptomatic respiratory treatments were: oxygen 81%, high-flow nasal canula oxygen 27%, non-invasive ventilation 36%, mechanical ventilation 64% and venovenous extracorporeal membrane oxygenation 18%. SLE-specific treatments were: corticosteroids 100%, cyclophosphamide 56% and plasma exchange 25%. All patients but one survived to ICU and hospital discharge. Two patients had a relapse of SLE-related ALD but none had interstitial lung disease during follow-up. CONCLUSION: Systemic lupus erythematosus-related acute respiratory failure is a severe event, mostly occurring at SLE onset, typical harboring a basal consolidation pattern on chest CT-scan and alveolar hemorrhage on BAL pathological examination. Mortality in our cohort is lower than previously reported but these results needs to be confirmed in further larger studies.

Identification of natural killer markers associated with fatal outcome in COVID-19 patients.

Introduction: Increasing evidence has shown that coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunological response. Previous studies have demonstrated that natural killer (NK) cell dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of NK cell markers as a driver of death in the most critically ill patients. Methods: We enrolled 50 non-vaccinated hospitalized patients infected with the initial virus or the alpha variant of SARS-CoV-2 with moderate or severe illness, to evaluate phenotypic and functional features of NK cells. Results: Here, we show that, consistent with previous studies, evolution NK cells from COVID-19 patients are more activated, with the decreased activation of natural cytotoxicity receptors and impaired cytotoxicity and IFN-γ production, in association with disease regardless of the SARS-CoV-2 strain. Fatality was observed in 6 of 17 patients with severe disease; NK cells from all of these patients displayed a peculiar phenotype of an activated memory-like phenotype associated with massive TNF-α production. Discussion: These data suggest that fatal COVID-19 infection is driven by an uncoordinated inflammatory response in part mediated by a specific subset of activated NK cells.

High-Dose Steroids for Nonresolving Acute Respiratory Distress Syndrome in Critically Ill COVID-19 Patients Treated With Dexamethasone: A Multicenter Cohort Study.

OBJECTIVES: To determine the impact of high doses of corticosteroids (HDCT) in critically ill COVID-19 patients with nonresolving acute respiratory distress syndrome (ARDS) who had been previously treated with dexamethasone as a standard of care. DESIGN: Prospective observational cohort study. Eligible patients presented nonresolving ARDS related to severe acute respiratory syndrome coronavirus 2 infection and had received initial treatment with dexamethasone. We compared patients who had received or not HDCT during ICU stay, consisting of greater than or equal to 1 mg/kg of methylprednisolone or equivalent for treatment of nonresolving ARDS. The primary outcome was 90-day mortality. We assessed the impact of HDCT on 90-day mortality using univariable and multivariable Cox regression analysis. Further adjustment for confounding variables was performed using overlap weighting propensity score. The association between HDCT and the risk of ventilator-associated pneumonia was estimated using multivariable cause-specific Cox proportional hazard model adjusting for pre-specified confounders. SETTING: We included consecutive patients admitted in 11 ICUs of Great Paris area from September 2020 to February 2021. PATIENTS: Three hundred eighty-three patients were included (59 in the HDCT group, 324 in the no HDCT group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At day 90, 30 of 59 patients (51%) in the HDCT group and 116 of 324 patients (35.8%) in the no HDCT group had died. HDCT was significantly associated with 90-day mortality in unadjusted (hazard ratio [HR], 1.60; 95% CI, 1.04-2.47; p = 0.033) and adjusted analysis with overlap weighting (adjusted HR, 1.65; 95% CI, 1.03-2.63; p = 0.036). HDCT was not associated with an increased risk of ventilator-associated pneumonia (adjusted cause-specific HR, 0.42; 95% CI, 0.15-1.16; p = 0.09). CONCLUSIONS: In critically ill COVID-19 patients with nonresolving ARDS, HDCT result in a higher 90-day mortality.