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.

Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial.

INTRODUCTION: Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation. METHODS AND ANALYSIS: The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation. ETHICS AND DISSEMINATION: The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III-PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04273360.

Association of socioeconomic deprivation with outcomes in critically ill adult patients: an observational prospective multicenter cohort study.

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

Effect of volume infusion on left atrial strain in acute circulatory failure.

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

Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial.

INTRODUCTION: Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever. METHODS AND ANALYSIS: SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients. ETHICS AND DISSEMINATION: The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04494074.

Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Low-flow ECCO2R conjoined with renal replacement therapy platform to manage pulmonary vascular dysfunction with refractory hypercapnia in ARDS.

Background: Hypercapnia worsens lung vascular dysfunction during acute respiratory distress syndrome (ARDS). We tested whether an extracorporeal carbon dioxide removal (ECCO2R) device based on a renal replacement therapy platform (Prismalung®) may reduce PaCO2 and alleviate lung vascular dysfunction in ARDS patients with refractory hypercapnia. Methods: We planned to prospectively include 20 patients with moderate-to-severe ARDS, pulmonary vascular dysfunction on echocardiography, and PaCO2 ≥ 48 mmHg despite instrumental dead space reduction and the increase in respiratory rate. Hemodynamics, echocardiography, respiratory mechanics, and arterial blood gases were recorded at 2 (H2), 6 (H6) and 24 (H24) hours as ECCO2R treatment was continued for at least 24 h. Results: Only eight patients were included, and the study was stopped due to worldwide shortage of ECCO2R membranes and the pandemic. Only one patient fulfilled the primary endpoint criterion (decrease in PaCO2 of more than 20 %) at H2, but this objective was achieved in half of patients (n = 4) at H6. The percentage of patients with a PaCO2 value < 48 mmHg increased with time, from 0/8 (0 %) at H0, to 3/8 (37.5 %) at H2 and 4/8 (50 %) at H6 (p = 0.04). There was no major change in hemodynamic and echocardiographic variables with ECCO2R, except for a significant decrease in heart rate. ECCO2R was prematurely discontinued before H24 in five (62.5 %) patients, due to membrane clotting in all cases. Conclusions: This pilot study testing showed a narrow efficacy and high rate of membrane thrombosis with the first version of the system. Improved versions should be tested in future trials. Trial registration: Registered at clinicaltrials.gov, identifier: NCT03303807, Registered: October 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03303807.

Biofilm Assessment and Metagenomic Analysis of Venoarterial Extracorporeal Membrane Oxygenation Cannulas and Membrane Oxygenators.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) exposes the patient to infectious complications related to the cannulas or the site of insertion. The aim of the current study was to investigate and compare the prevalence of cannula and membrane oxygenators colonization using three different methods: microbiological culture, scanning electron microscopy, and metagenomic (rRNA 16S analysis). A monocentric prospective study was conducted between December 2017 and June 2018. Consecutive patients undergoing VA-ECMO support for refractory cardiac arrest or cardiogenic shock were included. Ten patients were included with a median age of 64 (52-62) years. Venoarterial extracorporeal membrane oxygenation was inserted for refractory cardiac arrest in five (50%), cardiogenic shock in four (40%), and self-poisoning in one (10%) cases. Microbiological culture of all (8/8, 100%) membrane oxygenators was negative, whereas all (10/10, 100%) were colonized by biofilm, and eight (8/9, 89%) presented bacterial DNA. Three (3/9, 33%) arterial and venous cannulas were positive in culture and seven (7/9, 78%) were colonized by biofilm, respectively. Seven (7/9, 78%) arterial and four (4/9, 44%) venous cannulas presented bacterial DNA. Colonization of cannulas and membranes is more frequent when assessed by electron microscopy or metagenomic analysis than with culture. Membrane oxygenators are more often colonized than cannulas.

Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in critically ill COVID-19 patients.

Severe coronavirus disease 2019 (COVID-19) is related to dysregulated immune responses. We aimed to explore the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on the immune response by nasopharyngeal transcriptomic in critically-ill patients. This prospective monocentric study included COVID-19 patients requiring intensive care unit (ICU) admission between March 2020 and 2022. Patients were classified according to VOC (ancestral, Alpha, Delta, and Omicron). Eighty-eight patients with severe COVID-19 were included after matching (on prespecified clinical criteria). Profiling of gene expression markers of innate and adaptive immune responses were investigated by respiratory transcriptomics at ICU admission. Eighty-eight patients were included in the study after matching (ancestral [n = 24], Alpha [n = 24], Delta [n = 22], and Omicron [n = 18] variants). Respiratory transcriptomic analysis revealed distinct innate and adaptive immune profiling between variants. In comparison with the ancestral variant, there was a reduced expression of neutrophil degranulation, T cell activation, cytokines signalling pathways in patients infected with Alpha and Delta variants. In contrast, there was a higher expression of neutrophil degranulation, T and B cells activation, and inflammatory interleukins pathways in patients infected with Omicron. To conclude, Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in patients with severe COVID-19, pointing to an evolving pathophysiology of severe COVID-19 in the Omicron era.

Chest Computed Tomography Characteristics of Critically Ill COVID-19 Patients with Auto-antibodies Against Type I Interferons.

PURPOSE: Patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. METHODS: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. RESULTS: Two hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8) versus 24.0 (19.0-30.0), p = 0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175). CONCLUSION: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.

Influence of different noninvasive oxygenation support devices on tidal volume.

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

In-hospital outcomes after acute myocardial infarction with obstructive coronary artery disease in critically ill patients hospitalized for non-cardiac disease.

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

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

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.

Chest computed tomography characteristics of critically ill COVID-19 patients with auto-antibodies against type I interferons.

Purpose: patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. Methods: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (±72h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. Results: 231 critically ill COVID-19 patients were included in the study (mean age 59.5±12.7 years; males 74.6%). Day 90 mortality was 29.5% (n=72/244). There was a trend towards more severe radiological lesions in patients with auto-IFN anti-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8] versus 24.0 (19.0-30.0), p=0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p=0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p=0.623, n=175). Conclusion: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

A novel method for assessment of airway opening pressure without the need for low-flow insufflation.

BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.

A new reservoir-based CPAP with low oxygen consumption: the Bag-CPAP.

BACKGROUND: Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir ("Bag-CPAP") designed to minimize oxygen consumption, and compared it with other CPAP devices. METHODS: First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator. Two FiO2 targets (40-60% and 80-100%) at a predefined positive end expiratory pressure (PEEP) level between 5 and 10 cm H2O were tested and fraction of inspired oxygen (FiO2) and oxygen consumption were measured. Device-imposed work of breathing (WOB) was also evaluated. Second, an observational clinical study evaluated the new CPAP in 20 adult patients with acute respiratory failure in two hospitals in France. Actual FiO2, PEEP, peripheral oxygen saturation, respiratory rate, and dyspnea score were assessed. RESULTS: All six systems tested in the bench study reached the minimal FiO2 target of 40% and four reached at least 80% FiO2 while maintaining PEEP in the predefined range. Device-delivered FiO2/consumed oxygen ratio was the highest with the new reservoir-based CPAP irrespective of FiO2 target. WOB induced by the device was higher with Bag-CPAP. In the clinical study, Bag-CPAP was well tolerated and could reach high (> 90%) and moderate (> 50%) FiO2 with an oxygen flow rate of 15 [15-16] and 8 [7-9] L/min, respectively. Dyspnea score improved significantly after introduction of Bag-CPAP, and SpO2 increased. CONCLUSIONS: In vitro, Bag-CPAP exhibited the highest oxygen saving properties albeit had increased WOB. It was well accepted clinically and reduced dyspnea. Bag-CPAP may be useful to treat patients with acute respiratory failure in the field, especially when facing constraints in oxygen delivery.