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1.
International Journal of Environmental Research and Public Health ; 19(9):4978, 2022.
Article in English | MDPI | ID: covidwho-1792673

ABSTRACT

Delirium and psychomotor agitation are relevant clinical conditions that may develop during COVID-19 infection, especially in intensive care unit (ICU) settings. The psychopharmacological management of these conditions is receiving increasing interest in psychiatry, considering hyperkinetic delirium as one of the most common neuropsychiatries acute consequences in COVID-19 recovery patients. However, there are no actual internationally validated guidelines about this topic, due to the relatively newly introduced clinical condition;in addition, a standardized psychopharmacologic treatment of these cases is a complex goal to achieve due to the risk of both drug–drug interactions and the vulnerable conditions of those patients. The aim of this systematic review and case series is to evaluate and gather the scientific evidence on pharmacologic handling during delirium in COVID-19 patients to provide practical recommendations on the optimal management of psychotropic medication in these kinds of patients. The electronic databases PubMed, Embase and Web of Science were reviewed to identify studies, in accordance with the PRISMA guidelines. At the end of the selection process, a total of 21 studies (n = 2063) were included. We also collected a case series of acute psychomotor agitation in COVID-19 patients hospitalized in ICU. Our results showed how the symptom-based choice of the psychotropic medication is crucial, and even most of the psychotropic drug classes showed good safety, one must not underestimate the possible drug interactions and also the possible decrease in vital functions which need to be strictly monitored especially during treatment with some kinds of molecules. We believe that the evidence-based recommendations highlighted in the present research will enhance the current knowledge and could provide better management of these patients.

2.
Journal of Fungi ; 8(4):415, 2022.
Article in English | MDPI | ID: covidwho-1792631

ABSTRACT

Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated.

4.
Antibiotics (Basel) ; 11(1)2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1636790

ABSTRACT

Cefiderocol use in A. baumannii pneumonia still represents an important matter of debate. The aim of this study is to describe 13 cases of carbapenem-resistant A. baumannii (CRAB) pneumonia treated with cefiderocol in real-life practice. We retrospectively included patients with CRAB pneumonia hospitalized at Fondazione Policlinico Universitario Agostino Gemelli Hospital treated with cefiderocol either in the general ward or the intensive care unit. A total of 11 patients out of 13 had ventilator-associated pneumonia caused by CRAB, and 12/13 patients had polymicrobial infection. We found a 30-day success rate of 54%. Cefiderocol may have a role when facing severe XDR A. baumannii pneumonia. Future studies are warranted to better define its place in therapy in CRAB infections.

5.
Respir Physiol Neurobiol ; 298: 103844, 2022 04.
Article in English | MEDLINE | ID: covidwho-1620996

ABSTRACT

BACKGROUND: Use of high positive end-expiratory pressure (PEEP) and prone positioning is common in patients with COVID-19-induced acute respiratory failure. Few data clarify the hemodynamic effects of these interventions in this specific condition. We performed a physiologic study to assess the hemodynamic effects of PEEP and prone position during COVID-19 respiratory failure. METHODS: Nine adult patients mechanically ventilated due to COVID-19 infection and fulfilling moderate-to-severe ARDS criteria were studied. Respiratory mechanics, gas exchange, cardiac output, oxygen consumption, systemic and pulmonary pressures were recorded through pulmonary arterial catheterization at PEEP of 15 and 5 cmH2O, and after prone positioning. Recruitability was assessed through the recruitment-to-inflation ratio. RESULTS: High PEEP improved PaO2/FiO2 ratio in all patients (p = 0.004), and significantly decreased pulmonary shunt fraction (p = 0.012), regardless of lung recruitability. PEEP-induced increases in PaO2/FiO2 changes were strictly correlated with shunt fraction reduction (rho=-0.82, p = 0.01). From low to high PEEP, cardiac output decreased by 18 % (p = 0.05) and central venous pressure increased by 17 % (p = 0.015). As compared to supine position with low PEEP, prone positioning significantly decreased pulmonary shunt fraction (p = 0.03), increased PaO2/FiO2 (p = 0.03) and mixed venous oxygen saturation (p = 0.016), without affecting cardiac output. PaO2/FiO2 was improved by prone position also when compared to high PEEP (p = 0.03). CONCLUSIONS: In patients with moderate-to-severe ARDS due to COVID-19, PEEP and prone position improve arterial oxygenation. Changes in cardiac output contribute to the effects of PEEP but not of prone position, which appears the most effective intervention to improve oxygenation with no hemodynamic side effects.


Subject(s)
Blood Pressure/physiology , COVID-19/physiopathology , COVID-19/therapy , Heart Rate/physiology , Outcome and Process Assessment, Health Care , Oxygen Consumption/physiology , Positive-Pressure Respiration , Prone Position , Vascular Resistance/physiology , Aged , Aged, 80 and over , Female , Hemodynamic Monitoring , Humans , Intensive Care Units , Italy , Male , Middle Aged , Prone Position/physiology
6.
Microbiol Spectr ; 9(3): e0069521, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1597074

ABSTRACT

Bacterial pneumonia is a challenging coronavirus disease 2019 (COVID-19) complication for intensive care unit (ICU) clinicians. Upon its implementation, the FilmArray pneumonia plus (FA-PP) panel's practicability for both the diagnosis and antimicrobial therapy management of bacterial pneumonia was assessed in ICU patients with COVID-19. Respiratory samples were collected from patients who were mechanically ventilated at the time bacterial etiology and antimicrobial resistance were determined using both standard-of-care (culture and antimicrobial susceptibility testing [AST]) and FA-PP panel testing methods. Changes to targeted and/or appropriate antimicrobial therapy were reviewed. We tested 212 samples from 150 patients suspected of bacterial pneumonia. Etiologically, 120 samples were positive by both methods, two samples were culture positive but FA-PP negative (i.e., negative for on-panel organisms), and 90 were negative by both methods. FA-PP detected no culture-growing organisms (mostly Staphylococcus aureus or Pseudomonas aeruginosa) in 19 of 120 samples or antimicrobial resistance genes in two culture-negative samples for S. aureus organisms. Fifty-nine (27.8%) of 212 samples were from empirically treated patients. Antibiotics were discontinued in 5 (33.3%) of 15 patients with FA-PP-negative samples and were escalated/deescalated in 39 (88.6%) of 44 patients with FA-PP-positive samples. Overall, antibiotics were initiated in 87 (72.5%) of 120 pneumonia episodes and were not administered in 80 (87.0%) of 92 nonpneumonia episodes. Antimicrobial-resistant organisms caused 78 (60.0%) of 120 episodes. Excluding 19 colistin-resistant Acinetobacter baumannii episodes, AST confirmed appropriate antibiotic receipt in 101 (84.2%) of 120 episodes for one or more FA-PP-detected organisms. Compared to standard-of-care testing, the FA-PP panel may be of great value in the management of COVID-19 patients at risk of developing bacterial pneumonia in the ICU. IMPORTANCE Since bacterial pneumonia is relatively frequent, suspicion of it in COVID-19 patients may prompt ICU clinicians to overuse (broad-spectrum) antibiotics, particularly when empirical antibiotics do not cover the suspected pathogen. We showed that a PCR-based, culture-independent laboratory assay allows not only accurate diagnosis but also streamlining of antimicrobial therapy for bacterial pneumonia episodes. We report on the actual implementation of rapid diagnostics and its real-life impact on patient treatment, which is a gain over previously published studies on the topic. A better understanding of the role of that or similar PCR assays in routine ICU practice may lead us to appreciate the effectiveness of their implementation during the COVID-19 pandemic.


Subject(s)
COVID-19/complications , Hospitals , Multiplex Polymerase Chain Reaction/methods , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapy , Aged , Anti-Bacterial Agents/therapeutic use , Bacteria/genetics , COVID-19/diagnosis , COVID-19 Testing/methods , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Patient Acuity , Pneumonia, Bacterial/microbiology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
7.
Montalto, Francesca, Ippolito, Mariachiara, Noto, Alberto, Madotto, Fabiana, Gelardi, Filippa, Savatteri, Paolino, Giarratano, Antonino, Cortegiani, Andrea, Brescia, Fabrizio, Fabiani, Fabio, Zanier, Chiara, Nadalini, Elisa, Gambaretti, Eros, Gabriele, Francesco, Astuto, Marinella, Murabito, Paolo, Sanfilippo, Filippo, Misseri, Giovanni, Moscarelli, Alessandra, Spadaro, Savino, Bussolati, Enrico, Squadrani, Eleonora, Villa, Gianluca, D’Errico, Raffaella, Cocci, Giulia, Lanini, Iacopo, Mirabella, Lucia, Morelli, Alessandra, Tullo, Livio, Caggianelli, Girolamo, Ball, Lorenzo, Iiriti, Margherita, Giordani, Francesca, Giardina, Massimiliano, Mazzeo, Anna Teresa, Grasselli, Giacomo, Cattaneo, Emanuele, Alongi, Salvatore, Marenghi, Cristina, Marmiere, Marilena, Rocchi, Margherita, Turi, Stefano, Landoni, Giovanni, Torrano, Vito, Tinti, Giulia, Giorgi, Antonio, Fumagalli, Roberto, Salvo, Francesco, Blangetti, Ilaria, Cascella, Marco, Forte, Cira Antonietta, Navalesi, Paolo, Montalbano, Marta, Chiarelli, Valentina, Bonanno, Giuseppe, Ferrara, Francesco Paolo, Pernice, Innocenza, Catalisano, Giulia, Marino, Claudia, Presti, Gabriele, Fricano, Dario Calogero, Fucà, Rosa, Palmeri di Villalba, Cesira, Strano, Maria Teresa, Caruso, Sabrina, Scafidi, Antonino, Mazzarese, Vincenzo, Augugliaro, Ettore, Terranova, Valeria, Forfori, Francesco, Corradi, Francesco, Taddei, Erika, Isirdi, Alessandro, Pratesi, Giorgia, Puccini, Francesca, Paternoster, Gianluca, Barile, Alessio, Tescione, Marco, Santacaterina, Irene, Siclari, Eliana Maria, Tripodi, Vincenzo Francesco, Vadalà, Mariacristina, Agrò, Felice Eugenio, Pascarella, Giuseppe, Piliego, Chiara, Aceto, Paola, De Pascale, Gennaro, Dottarelli, Alessandra, Romanò, Bruno, Russo, Andrea, Covotta, Marco, Giorgerini, Valeria, Sardellitti, Federica, Vitelli, Giulia Maria, Coluzzi, Flaminia, Bove, Tiziana, Vetrugno, Luigi.
Journal of Anesthesia, Analgesia and Critical Care ; 1(1):17-17, 2021.
Article in English | BioMed Central | ID: covidwho-1542137
8.
ERJ Open Res ; 7(4)2021 Oct.
Article in English | MEDLINE | ID: covidwho-1526593

ABSTRACT

In #COVID19 patients, presence of moderate-to-severe dyspnoea is a marker of disease severity correlated to clinical outcomes https://bit.ly/3Bp2G1b.

9.
Eur J Clin Invest ; 51(12): e13687, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1443255

ABSTRACT

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.


Subject(s)
COVID-19/prevention & control , Cross Infection/epidemiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Infection Control , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter Infections/transmission , Acinetobacter baumannii , Aged , Cross Infection/microbiology , Cross Infection/transmission , Drug Resistance, Multiple, Bacterial , Enterobacter , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/transmission , Enterococcus faecium , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/transmission , Female , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/transmission , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/transmission , Hand Disinfection , Humans , Intensive Care Units , Interrupted Time Series Analysis , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella Infections/transmission , Klebsiella pneumoniae , Male , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Organizational Policy , Personal Protective Equipment , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas Infections/transmission , Pseudomonas aeruginosa , Retrospective Studies , SARS-CoV-2 , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/transmission , Staphylococcus aureus , Visitors to Patients
10.
EClinicalMedicine ; 27: 100553, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1385448

ABSTRACT

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

11.
Minerva Anestesiol ; 87(10): 1080-1090, 2021 10.
Article in English | MEDLINE | ID: covidwho-1337893

ABSTRACT

BACKGROUND: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model. RESULTS: Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS: Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Compassionate Use Trials , Critical Illness , Humans , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
12.
Minerva Anestesiol ; 87(9): 1006-1016, 2021 09.
Article in English | MEDLINE | ID: covidwho-1311484

ABSTRACT

BACKGROUND: The aim of this study is 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.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Adult , Humans , Lung/diagnostic imaging , Pilot Projects , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/therapy , SARS-CoV-2
13.
Crit Care ; 25(1): 197, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1261277

ABSTRACT

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, R2 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 (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 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.


Subject(s)
COVID-19/complications , Pneumonia, Ventilator-Associated/microbiology , Staphylococcal Infections/etiology , Staphylococcus aureus/isolation & purification , Aged , Anti-Bacterial Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Italy , Logistic Models , Lung/microbiology , Male , Middle Aged , Organ Dysfunction Scores , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/etiology , Prospective Studies , Respiration, Artificial , Staphylococcal Infections/drug therapy
14.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1241490

ABSTRACT

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.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
16.
Chest ; 160(2): 454-465, 2021 08.
Article in English | MEDLINE | ID: covidwho-1184884

ABSTRACT

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 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 double mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov.


Subject(s)
COVID-19/complications , Cross Infection/complications , Aged , Critical Illness , Cross Infection/epidemiology , Female , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/complications , Pneumonia, Ventilator-Associated/epidemiology , Retrospective Studies , Sepsis/complications , Sepsis/epidemiology
17.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1148761

ABSTRACT

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.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
18.
Respir Care ; 66(5): 705-714, 2021 05.
Article in English | MEDLINE | ID: covidwho-1115489

ABSTRACT

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 (P = .009) and serum lactate dehydrogenase at enrollment (P = .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%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .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.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Critical Illness , Humans , Hypoxia/etiology , Hypoxia/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2
20.
Crit Care ; 24(1): 529, 2020 08 28.
Article in English | MEDLINE | ID: covidwho-733031

ABSTRACT

BACKGROUND: Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. METHODS: Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. RESULTS: Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO2/FiO2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH2O [32-52] vs. 36 ml/cmH2O [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. CONCLUSIONS: Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Respiratory Distress Syndrome/physiopathology , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/therapy , Female , Humans , Intensive Care Units , Italy , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Function Tests , Respiratory Mechanics/physiology , SARS-CoV-2
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