Publications by authors named "Massimo Antonelli"

340 Publications

Prolonged Stress Causes Depression in Frontline Workers Facing the COVID-19 Pandemic-A Repeated Cross-Sectional Study in a COVID-19 Hub-Hospital in Central Italy.

Int J Environ Res Public Health 2021 Jul 8;18(14). Epub 2021 Jul 8.

Department of Emergency, Anesthesiology and Resuscitation Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.

The COVID-19 pandemic has severely tested the mental health of frontline health care workers. A repeated cross-sectional study can provide information on how their mental health evolved during the various phases of the pandemic. The intensivists of a COVID-19 hub hospital in Rome were investigated with a baseline survey during the first wave of the pandemic in April 2020, and they were contacted again in December 2020, during the second wave. Of the 205 eligible workers, 152 responded to an online questionnaire designed to measure procedural justice, occupational stress (effort/reward imbalance), sleep quality, anxiety, depression, burnout, job satisfaction, happiness, and turnover intention. Workers reported a further increase in workload and compassion fatigue, which had already risen during the first wave, and a marked reduction in the time devoted to meditation and mental activities. A low level of confidence in the adequacy of safety procedures and the need to work in isolation, together with an increased workload and lack of time for meditation, were the most significant predictors of occupational stress in a stepwise linear regression model. Occupational stress was, in turn, a significant predictor of insomnia, anxiety, low job satisfaction, burnout, and intention to leave the hospital. The number of workers manifesting symptoms of depression increased significantly to exceed 60%. Action to prevent occupational risks and enhance individual resilience cannot be postponed.
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http://dx.doi.org/10.3390/ijerph18147316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304927PMC
July 2021

Lung ultrasound predicts non-invasive ventilation outcome in COVID-19 acute respiratory failure: a pilot study.

Minerva Anestesiol 2021 Jul 14. Epub 2021 Jul 14.

Intensive Care Unit, Department of Emergency, Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: To determine relationships between lung aeration assessed by lung ultrasound (LUS) with Non-Invasive Ventilation (NIMV) outcome, intensive care unit (ICU) admission and mechanical ventilation (MV) needs in COVID-19 respiratory failure.

Methods: A cohort of adult patients with COVID-19 respiratory failure underwent LUS during initial assessment. A simplified LUS protocol consisting in scanning six areas, three for each side, was adopted. A score from 0 to 3 was assigned to each area. Comprehensive LUS score (LUSsc) was calculated as the sum of the score in all areas. LUSsc, the amount of involved sonographic lung areas (LUSq), the number of lung quadrants radiographically infiltrated and the degree of oxygenation impairment at admission (SpO2/FiO2 ratio) were compared to NIMV Outcome, MV needs and ICU admission.

Results: Among 85 patients prospectively included in the analysis, 49 of 61 needed MV. LUSsc and LUSq were higher in patients who required MV (median 12 [IQR 8-14] and median 6 [IQR 4-6], respectively) than in those who did not (6 [IQR 2-9] and 3 [IQR 1-5], respectively), both p < 0.001. NIMV trial failed in 26 patients out 36. LUSsc and LUSq were significantly higher in patients who failed NIMV than in those who did not. From ROC analysis, LUSsc ≧ 12 and LUSq ≧5 gave the best cut-off values for NIMV failure prediction (AUC=0.95, 95%CI 0.83-0.99 and AUC=0.81, 95%CI 0.65-0.91, respectively).

Conclusions: Our data suggest LUS as a possible tool for identifying patients who are likely to require MV and ICU admission or to fail a NIMV trial.
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http://dx.doi.org/10.23736/S0375-9393.21.15188-0DOI Listing
July 2021

Non-invasive ventilatory support and high-flow nasal oxygen as first-line treatment of acute hypoxemic respiratory failure and ARDS.

Intensive Care Med 2021 Aug 7;47(8):851-866. Epub 2021 Jul 7.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

The role of non-invasive respiratory support (high-flow nasal oxygen and noninvasive ventilation) in the management of acute hypoxemic respiratory failure and acute respiratory distress syndrome is debated. The oxygenation improvement coupled with lung and diaphragm protection produced by non-invasive support may help to avoid endotracheal intubation, which prevents the complications of sedation and invasive mechanical ventilation. However, spontaneous breathing in patients with lung injury carries the risk that vigorous inspiratory effort, combined or not with mechanical increases in inspiratory airway pressure, produces high transpulmonary pressure swings and local lung overstretch. This ultimately results in additional lung damage (patient self-inflicted lung injury), so that patients intubated after a trial of noninvasive support are burdened by increased mortality. Reducing inspiratory effort by high-flow nasal oxygen or delivery of sustained positive end-expiratory pressure through the helmet interface may reduce these risks. In this physiology-to-bedside review, we provide an updated overview about the role of noninvasive respiratory support strategies as early treatment of hypoxemic respiratory failure in the intensive care unit. Noninvasive strategies appear safe and effective in mild-to-moderate hypoxemia (PaO/FiO > 150 mmHg), while they can yield delayed intubation with increased mortality in a significant proportion of moderate-to-severe (PaO/FiO ≤ 150 mmHg) cases. High-flow nasal oxygen and helmet noninvasive ventilation represent the most promising techniques for first-line treatment of severe patients. However, no conclusive evidence allows to recommend a single approach over the others in case of moderate-to-severe hypoxemia. During any treatment, strict physiological monitoring remains of paramount importance to promptly detect the need for endotracheal intubation and not delay protective ventilation.
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http://dx.doi.org/10.1007/s00134-021-06459-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261815PMC
August 2021

Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemic and standard interfaces for non-invasive ventilation.

Pulmonology 2021 Jun 8. Epub 2021 Jun 8.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: The aim of this bench study is to compare the standard NIV and nCPAP devices (Helmet, H; Full face mask, FFM) with a modified full face snorkeling mask used during COVID-19 pandemic.

Methods: A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort, were determined relative to the preset CPAP level. NIV was applied in Pressure Support Mode at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study, we measured the variables defining patient-ventilator interaction and performance.

Results: During nCPAP, the tested interfaces did not show significant differences in terms of ∆Pawi and ∆Pawe. During NIV, the snorkeling mask demonstrated a better patient-ventilator interaction compared to FFM, as shown by significantly shorter Pressurization Time and Expiratory Trigger Delay (p < 0.01), but no significant differences were found in terms of Inspiratory Trigger Delay and Time of Synchrony between the interfaces tested. At RR 20sim, the snorkeling mask presented the lower ΔPtrigger (p < 0.01), moreover during all the conditions tested the snorkeling mask showed the longer Pressure Time Product at 200, 300, and 500 ms compared to FFM (p < 0.01). A major limitation of snorkeling mask is that during NIV with this interface it is possible to reach maximum 18 cmHO of peak inspiratory pressure.

Conclusions: The modified snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergencies.
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http://dx.doi.org/10.1016/j.pulmoe.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185250PMC
June 2021

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

Crit Care 2021 06 26;25(1):219. Epub 2021 Jun 26.

Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.

Background: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients.

Methods: Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed.

Results: Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72-0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001).

Conclusion: DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.
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http://dx.doi.org/10.1186/s13054-021-03638-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233594PMC
June 2021

COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.

JCI Insight 2021 06 18;6(13). Epub 2021 Jun 18.

Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.
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http://dx.doi.org/10.1172/jci.insight.147413DOI Listing
June 2021

Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation.

Crit Care 2021 06 7;25(1):196. Epub 2021 Jun 7.

Department of Anesthesia and Intensive Care, Fondazione Poliambulanza, Brescia, Italy.

Background: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient's inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation.

Methods: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume.

Results: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods.

Conclusions: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions.
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http://dx.doi.org/10.1186/s13054-021-03624-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182360PMC
June 2021

Staphylococcus aureus ventilator-associated pneumonia in patients with COVID-19: clinical features and potential inference with lung dysbiosis.

Crit Care 2021 06 7;25(1):197. Epub 2021 Jun 7.

Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.

Methods: We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.

Results: We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log fold change, 29.5), Streptococcus anginosus subspecies anginosus (log fold change, 24.9), and Olsenella (log fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients.

Conclusions: In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.
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http://dx.doi.org/10.1186/s13054-021-03623-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182737PMC
June 2021

Finding an Evidence-Based and Clinically Important Role for BAL in the Setting of Suspected SARS-Cov-2 Infection.

Chest 2021 04 6;159(4):1680-1681. Epub 2021 Apr 6.

Department of Anaesthesia and Intensive Care, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.1016/j.chest.2020.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021942PMC
April 2021

BMI and pneumonia outcomes in critically ill COVID-19 patients: an international multicenter study.

Obesity (Silver Spring) 2021 May 9. Epub 2021 May 9.

Intensive Care Unit, Centre hospitalier de Dunkerque, 59240, Dunkerque.

Background: Previous studies unveiled a relation between the severity of COVID-19 pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, current smoking) in critically ill patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled patients admitted in intensive care for COVID-19, in 21 centers (Europe, Israel, USA) between 02/19/2020 and 05/19/2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV), and 28-day mortality.

Results: A total of 1,461 patients were enrolled, median(IQR) age was 64 years (40.9-72.0); 73.2% males; BMI 28.1 kg/m (25.4-32.3); 1,080 patients (73.9%) required IMV; the 28-day mortality estimate was 36.1% (95%CI, 33.0-39.5). Adjusted mixed logistic regression model showed a significant linear relation between BMI and IMV: OR 1.27 (95%CI, 1.12-1.45) per 5 kg/m . Adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was only increased in obesity class III (≥40 kg/m ) (HR 1.68 (95%CI 1.06-2.64).

Conclusion: In critically ill COVID-19 patients, we observed a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a non-linear association between BMI and mortality risk. (NCT04391738).
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http://dx.doi.org/10.1002/oby.23223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242742PMC
May 2021

COVID-19 influences lung microbiota dynamics and favors the emergence of rare infectious diseases: A case report of Hafnia Alvei pneumonia.

J Crit Care 2021 08 18;64:173-175. Epub 2021 Apr 18.

Dipartimento di Scienze dell' Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Facoltà di medicina e chirurgia "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.

The coronavirus disease 2019 causes a wide degree of organ dysfunction and is associated with bacterial secondary infections. We reported lung microbiota dynamics in a critically ill patient with coronavirus disease 2019, who developed severe Hafnia alvei ventilator-associated pneumonia and required extracorporeal membrane oxygenation support.
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http://dx.doi.org/10.1016/j.jcrc.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053226PMC
August 2021

Personalized Clinical Phenotyping through Systems Medicine and Artificial Intelligence.

J Pers Med 2021 Apr 2;11(4). Epub 2021 Apr 2.

Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Personalized Medicine (PM) has shifted the traditional top-down approach to medicine based on the identification of single etiological factors to explain diseases, which was not suitable for explaining complex conditions. The concept of PM assumes several interpretations in the literature, with particular regards to Genetic and Genomic Medicine. Despite the fact that some disease-modifying genes affect disease expression and progression, many complex conditions cannot be understood through only this lens, especially when other lifestyle factors can play a crucial role (such as the environment, emotions, nutrition, etc.). Personalizing clinical phenotyping becomes a challenge when different pathophysiological mechanisms underlie the same manifestation. Brain disorders, cardiovascular and gastroenterological diseases can be paradigmatic examples. Experiences on the field of Fondazione Policlinico Gemelli in Rome (a research hospital recognized by the Italian Ministry of Health as national leader in "Personalized Medicine" and "Innovative Biomedical Technologies") could help understanding which techniques and tools are the most performing to develop potential clinical phenotypes personalization. The connection between practical experiences and scientific literature highlights how this potential can be reached towards Systems Medicine using Artificial Intelligence tools.
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http://dx.doi.org/10.3390/jpm11040265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065854PMC
April 2021

Bacteremia in critically ill immunocompromised patients with acute hypoxic respiratory failure: A post-hoc analysis of a prospective multicenter multinational cohort.

J Crit Care 2021 Aug 17;64:114-119. Epub 2021 Apr 17.

Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France.

Purpose: The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF).

Methods: We performed a secondary analysis of a prospective cohort of immunocompromised patients with ARF (EFRAIM study). After exclusion of blood cultures positive for coagulase negative Staphylococci, we compared patients with (n = 236) and without (n = 1127) bacteremia.

Results: The incidence of bacteremia was 17%. Bacterial pneumonia and extra-pulmonary ARDS were the main causes of ARF in bacteremic patients. Bacteremia involved gram negative rods (48%), gram positive cocci (40%) or were polymicrobial (10%). Bacteremic patients had more hematological malignancy, higher SOFA scores and increased organ support within 7 days. Bacteremia was associated with higher crude ICU mortality (40% versus 32%, p = 0.02), but neither hospital (49% versus 44%, p = 0.17) nor 90-day mortality (60% versus 56%, p = 0.25) were different from non-bacteremic patients. After propensity score matching based on baseline characteristics, the difference in ICU mortality lost statistical significance (p = 0.06), including in a sensitivity analysis restricted to patients with pneumonia.

Conclusions: We analyzed a large population of immunocompromised patients with ARF and an incidence of bacteremia of 17%. We could not demonstrate an impact of bacteremia on mortality after adjusting for baseline characteristics.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.014DOI Listing
August 2021

Hospital-Acquired Infections in Critically Ill Patients With COVID-19.

Chest 2021 Apr 20. Epub 2021 Apr 20.

Department of Anaesthesia and Intensive Care, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Background: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19.

Research Question: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients?

Study Design And Methods: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs.

Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 patient intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001).

Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost doubled mortality.

Trial Registry: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056844PMC
April 2021

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

Crit Care 2021 04 6;25(1):128. Epub 2021 Apr 6.

Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.

Background: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave.

Methods: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO/FiO ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position.

Results: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO/FiO ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively).

Conclusions: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching.

Trial Registration: clinicaltrials.gov number: NCT04388670.
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http://dx.doi.org/10.1186/s13054-021-03552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022297PMC
April 2021

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

JAMA 2021 05;325(17):1731-1743

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario AGemelli IRCCS, Rome, Italy.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, Setting, And Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main Outcomes And Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99).

Conclusions And Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.
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http://dx.doi.org/10.1001/jama.2021.4682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995134PMC
May 2021

Effect of influenza vaccine on COVID-19 mortality: a retrospective study.

Intern Emerg Med 2021 Mar 20. Epub 2021 Mar 20.

Emergency Medicine Department, Fondazione Universitaria Policlinico Gemelli-IRCCS-Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00135, Rome, Italy.

It has been proposed that vaccines may exert an unspecific protective effect against infectious agents, different than expected. Coronavirus disease 2019 (COVID-19) is a pandemic infection with high mortality in older patients due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The high number of vaccinations may be one of the reasons why children show a lower susceptibility to SARS-CoV-2 infection and milder severity when compared to adults. We have designed a study aimed at investigating whether the influenza vaccine may reduce the susceptibility and severity of SARS-CoV-2 infection. We retrospectively enrolled 635 patients who accessed our Emergency Department from March 1st to June 30th, 2020, and were diagnosed with COVID-19 infection confirmed by an RT-PCR on an oropharyngeal swab. Clinical data, outcomes, and influenza vaccination status were collected from the electronic medical records of our Hospital. We also used data from the Italian Health Ministry to compare the prevalence of flu vaccination among the general population of the Lazio Region and our enrolled patients. We then compared clinical outcomes between vaccinated and non-vaccinated patients, by univariate and multivariate analysis. COVID-19-positive patients older than 65 years reported a lower prevalence of flu vaccination when compared to the general population residing in the Lazio (p = 0.004). After correction for gender, age, and comorbidities, we found a lower risk of death at 60 days in patients with flu vaccination than in not vaccinated patients (p = 0.001). Our study shows that flu vaccination could reduce the mortality of COVID-19. Prospective studies are needed to confirm this result.
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http://dx.doi.org/10.1007/s11739-021-02702-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980752PMC
March 2021

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

Crit Care 2021 03 16;25(1):106. Epub 2021 Mar 16.

Manchester University NHS Foundation Trust, Manchester, UK.

Background: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice.

Methods: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ) test (p < 0·05 was considered as unstable).

Results: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment.

Conclusion: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited.

Trial Registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.
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http://dx.doi.org/10.1186/s13054-021-03491-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962430PMC
March 2021

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

Respir Care 2021 05 2;66(5):705-714. Epub 2021 Mar 2.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS; Rome, Italy.

Background: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19.

Methods: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes.

Results: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score ( = .009) and serum lactate dehydrogenase at enrollment ( = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, = .01).

Conclusions: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.
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http://dx.doi.org/10.4187/respcare.08622DOI Listing
May 2021

Renin-angiotensin system dysregulation in critically ill patients with acute respiratory distress syndrome due to COVID-19: a preliminary report.

Crit Care 2021 03 1;25(1):91. Epub 2021 Mar 1.

Department of Intensive Care Medicine and Anesthesiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1186/s13054-021-03507-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919982PMC
March 2021

Multiple organ failure: incidence and outcomes over time.

Minerva Anestesiol 2021 02;87(2):139-141

Department of Intensive Care Medicine and Anesthesiology, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy.

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http://dx.doi.org/10.23736/S0375-9393.21.15446-XDOI Listing
February 2021

Respiratory mechanics heterogeneity is related to inflammatory biomarkers in acute respiratory distress syndrome due to COVID-19.

Minerva Anestesiol 2021 06 16;87(6):740-744. Epub 2021 Feb 16.

Department of Emergency, Intensive Care Medicine and Anesthesia, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

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http://dx.doi.org/10.23736/S0375-9393.21.15289-7DOI Listing
June 2021

The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

Crit Care Med 2021 04;49(4):598-622

Chirec Hospitals, Université Libre de Bruxelles, Brussels, Belgium.

Objectives: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients.

Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document.

Methods: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research.

Results: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given?

Conclusions: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCM.0000000000004895DOI Listing
April 2021

Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study.

Crit Care 2021 02 15;25(1):61. Epub 2021 Feb 15.

Department of Anesthesiology, Critical Care and Burn Center, Lariboisière - Saint-Louis Hospitals, DMU Parabol, AP-HP Nord, University of Paris, Paris, France.

Background: Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.

Methods: The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.

Results: Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.

Conclusions: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
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http://dx.doi.org/10.1186/s13054-021-03471-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885215PMC
February 2021

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

Crit Care Med 2021 03;49(3):e219-e234

Warren Alpert School of Medicine at Brown University, Providence, RI.

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
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http://dx.doi.org/10.1097/CCM.0000000000004899DOI Listing
March 2021

Instrumental dead space in ventilator management.

Lancet Respir Med 2021 03 29;9(3):e22. Epub 2021 Jan 29.

Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1016/S2213-2600(21)00024-2DOI Listing
March 2021

Noninvasive ventilation and high-flow oxygen therapy for severe community-acquired pneumonia.

Curr Opin Infect Dis 2021 04;34(2):142-150

Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8.

Purpose Of Review: We review the evidence on the use of noninvasive respiratory supports (noninvasive ventilation and high-flow nasal cannula oxygen therapy) in patients with acute respiratory failure because of severe community-acquired pneumonia.

Recent Findings: Noninvasive ventilation is strongly advised for the treatment of hypercapnic respiratory failure and recent evidence justifies its use in patients with hypoxemic respiratory failure when delivered by helmet. Indeed, such interface allows alveolar recruitment by providing high level of positive end-expiratory pressure, which improves hypoxemia. On the other hand, high-flow nasal cannula oxygen therapy is effective in patients with hypoxemic respiratory failure and some articles support its use in patients with hypercapnia. However, early identification of noninvasive respiratory supports treatment failure is crucial to prevent delayed orotracheal intubation and protective invasive mechanical ventilation.

Summary: Noninvasive ventilation is the first-line therapy in patients with acute hypercapnic respiratory failure because of pneumonia. Although an increasing amount of evidence investigated the application of noninvasive respiratory support to hypoxemic respiratory failure, the optimal ventilatory strategy in this setting is uncertain. Noninvasive mechanical ventilation delivered by helmet and high-flow nasal cannula oxygen therapy appear as promising tools but their role needs to be confirmed by future research.
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http://dx.doi.org/10.1097/QCO.0000000000000715DOI Listing
April 2021

Hemadsorption.

Curr Opin Anaesthesiol 2021 Apr;34(2):113-118

Unità Operativa Complessa di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica; Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Purpose Of Review: To review pathophysiological pathways of immune system response to infections, which may justify mediators removal by extracorporeal blood purification therapies (EBPTs) in critically ill septic patients. Moreover, we presented an overview of the EBPTs mostly used in clinical practice with the aim to modulate immune system dysfunction in sepsis.

Recent Findings: Sepsis is a life-threatening disease and recent findings showed that its pathophysiology relies on dysregulated immune system response to pathogen invasion of the body. In the light of this view, EBPTs have been demonstrated effective to remove specific mediators and foster balance between pro- and anti-inflammatory pathways.

Summary: EBPTs have been widely used in clinical practice, with the aim to modulate immune system dysfunction by the removal of pathogens and inflammatory mediators in critically ill patients with sepsis. Such therapies are characterised by specific structural features, which allow selective and nonselective removal of mediators by adsorption. However, few evidences support their role in the management of critically ill patients with sepsis. Accordingly, an evidence-based and personalized approach to EBPTs in sepsis is strongly advocated, in order to solve controversies in this field and optimise the management of critically ill septic patients.
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http://dx.doi.org/10.1097/ACO.0000000000000953DOI Listing
April 2021

Good clinical practice for the use of vasopressor and inotropic drugs in critically ill patients: state-of-the-art and expert consensus.

Minerva Anestesiol 2021 06 12;87(6):714-732. Epub 2021 Jan 12.

Department of Anesthesia and Intensive Care, Modena University Hospital, Modena, Italy.

Vasopressors and inotropic agents are widely used in critical care. However, strong evidence supporting their use in critically ill patients is lacking in many clinical scenarios. Thus, the Italian Society of Anesthesia and Intensive Care (SIAARTI) promoted a project aimed to provide indications for good clinical practice on the use of vasopressors and inotropes, and on the management of critically ill patients with shock. A panel of 16 experts in the field of intensive care medicine and hemodynamics has been established. Systematic review of the available literature was performed based on PICO questions. Basing on available evidence, the panel prepared a summary of evidence and then wrote the clinical questions. A modified semi-quantitative RAND/UCLA appropriateness method has been used to determine the appropriateness of specific clinical scenarios. The panel identified 29 clinical questions for the use of vasopressors and inotropes in patients with septic shock and cardiogenic shock. High level of agreement exists among the panel members about appropriateness of inotropes/vasopressors' use in patients with septic shock and cardiogenic shock.
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http://dx.doi.org/10.23736/S0375-9393.20.14866-1DOI Listing
June 2021

Polymyxin B hemoperfusion in coronavirus disease 2019 patients with endotoxic shock: Case series from EUPHAS2 registry.

Artif Organs 2021 Jun 17;45(6):E187-E194. Epub 2021 Feb 17.

International Renal Research Institute of Vicenza and Department of Nephrology, Dialysis and Transplantation and International Renal Research Institute of Vicenza, San Bortolo Hospital, Vicenza, Italy.

The coronavirus disease 2019 (COVID-19) has been shown to involve the gastrointestinal tract, which implies bacterial translocation and endotoxemia. The aim of this study was to evaluate the role of extracorporeal endotoxin removal by Polymyxin B hemoperfusion (PMX-HP), in the treatment of patients with COVID-19 and secondary bacterial infection. We conducted a subgroup analysis of a multicenter, multinational, prospective, and observational web-based database (EUPHAS2 registry). We included 12 patients with severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasal/oral swab, admitted to the intensive care unit between February and May 2020, who were affected by septic shock and received PMX-HP as per clinical indication of the attending physician. Septic shock was diagnosed in nine patients (75%), with a median time between symptoms onset and PMX-HP treatment of 16 (14-22) days. We identified Gram-negative bacteria in most of the microbiological cultures (N = 17, 65%), followed by Gram-positive bacteria in (N = 4, 15%), fungi (N = 3, 12%) and no growth (N = 2, 8%). Sequential Organ Failure Assessment (SOFA) score progressively improved over the next 120 hours following PMX-HP and it was associated with median endotoxin activity assay (EAA) decrease from 0.78 [0.70-0.92] at T0 to 0.60 [0.44-0.72] at T120 (P = .245). A direct correlation was observed between SOFA score and EAA. Lung Injury Score decreased and was associated with hemodynamic improvement over the same period. No statistically significant difference was observed for RIFLE score at each time point. Nine out of 12 patients (75%) required continuous renal replacement therapy because of acute kidney injury. In a series of consecutive COVID-19 patients with endotoxic shock, PMX-HP was associated with organ function recovery, hemodynamic improvement, and contemporary EAA level reduction. No PMX-HP-related complications were observed.
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http://dx.doi.org/10.1111/aor.13900DOI Listing
June 2021
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