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1. Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study

Author

Scaramuzzo G., Gamberini L., Tonetti T., Zani G., Ottaviani I., Mazzoli C. A., Capozzi C., Giampalma E., Bacchi Reggiani M. L., Bertellini E., Castelli A., Cavalli I., Colombo D., Crimaldi F., Damiani F., Fusari M., Gamberini E., Gordini G., Laici C., Lanza M. C., Leo M., Marudi A., Nardi G., Papa R., Potalivo A., Russo E., Taddei S., Consales G., Cappellini I., Ranieri V. M., Volta C. A., Guerin C., Spadaro S., Tartaglione M., Chiarini V., Buldini V., Coniglio C., Moro F., Barbalace C., Citino M., Cilloni N., Giuntoli L., Bellocchio A., Matteo E., Pizzilli G., Siniscalchi A., Tartivita C., Matteo F., Marchio A., Bacchilega I., Bernabe L., Guarino S., Mosconi E., Bissoni L., Viola L., Meconi T., Pavoni V., Pagni A., Pompa Cleta P., Cavagnino M., Malfatto A., Adduci A., Pareschi S., Melegari G., Maccieri J., Marinangeli E., Racca F., Verri M., Falo G., Marangoni E., Boni F., Felloni G., Baccarini F. D., Terzitta M., Maitan S., Becherucci F., Parise M., Masoni F., Imbriani M., Orlandi P., Monetti F., Dalpiaz G., Golfieri R., Ciccarese F., Poerio A., Muratore F., Ferrari F., Mughetti M., Franchini L., Neziri E., Miceli M., Minguzzi M. T., Mellini L., Piciucchi S., Bartolucci M., Scaramuzzo G., Gamberini L., Tonetti T., Zani G., Ottaviani I., Mazzoli C.A., Capozzi C., Giampalma E., Bacchi Reggiani M.L., Bertellini E., Castelli A., Cavalli I., Colombo D., Crimaldi F., Damiani F., Fusari M., Gamberini E., Gordini G., Laici C., Lanza M.C., Leo M., Marudi A., Nardi G., Papa R., Potalivo A., Russo E., Taddei S., Consales G., Cappellini I., Ranieri V.M., Volta C.A., Guerin C., Spadaro S., Tartaglione M., Chiarini V., Buldini V., Coniglio C., Moro F., Barbalace C., Citino M., Cilloni N., Giuntoli L., Bellocchio A., Matteo E., Pizzilli G., Siniscalchi A., Tartivita C., Matteo F., Marchio A., Bacchilega I., Bernabe L., Guarino S., Mosconi E., Bissoni L., Viola L., Meconi T., Pavoni V., Pagni A., Pompa Cleta P., Cavagnino M., Malfatto A., Adduci A., Pareschi S., Melegari G., Maccieri J., Marinangeli E., Racca F., Verri M., Falo G., Marangoni E., Boni F., Felloni G., Baccarini F.D., Terzitta M., Maitan S., Becherucci F., Parise M., Masoni F., Imbriani M., Orlandi P., Monetti F., Dalpiaz G., Golfieri R., Ciccarese F., Poerio A., Muratore F., Ferrari F., Mughetti M., Franchini L., Neziri E., Miceli M., Minguzzi M.T., Mellini L., Piciucchi S., and Bartolucci M.

Subjects
medicine.medical_specialty, Supine position, COVID19, medicine.medical_treatment, Respiratory physiology, Prone positioning, ventilatory free days, Critical Care and Intensive Care Medicine, ICU, COVID19, Prone positioning, ventilatory free days, NO, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, medicine, 030212 general & internal medicine, Mechanical ventilation, business.industry, RC86-88.9, Research, Medical emergencies. Critical care. Intensive care. First aid, Oxygenation, respiratory system, respiratory tract diseases, Prone position, 030228 respiratory system, Anesthesia, ICU, Complication, business, Cohort study
Abstract

Background Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation. Results The median PaO2/FiO2 variation after the first PP cycle was 49 [19–100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP. Conclusions Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.

Published
2021

2. Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs

Author

Gamberini, L., Tonetti, T., Spadaro, S., Zani, G., Mazzoli, C. A., Capozzi, C., Giampalma, E., Bacchi Reggiani, M. L., Bertellini, E., Castelli, A., Cavalli, I., Colombo, D., Crimaldi, F., Damiani, F., Fogagnolo, A., Fusari, M., Gamberini, E., Gordini, G., Laici, C., Lanza, M. C., Leo, M., Marudi, A., Nardi, G., Ottaviani, I., Papa, R., Potalivo, A., Russo, E., Taddei, S., Volta, C. A., Ranieri, V. M., Tartaglione, M., Chiarini, V., Buldini, V., Coniglio, C., Moro, F., Cilloni, N., Giuntoli, L., Bellocchio, A., Matteo, E., Pizzilli, G., Siniscalchi, A., Tartivita, C., Matteo, F., Marchio, A., Bacchilega, I., Bernabe, L., Guarino, S., Mosconi, G., Bissoni, L., Viola, L., Meconi, T., Pavoni, V., Pagni, A., Pompacleta, P., Cavagnino, M., Malfatto, A., Adduci, A., Pareschi, S., Melegari, G., Maccieri, J., Marinangeli, E., Racca, F., Verri, M., Falo, G., Marangoni, E., Boni, F., Felloni, G., Baccarini, F. D., Terzitta, M., Maitan, S., Imbriani, M., Orlandi, P., Dalpiaz, G., Golfieri, R., Ciccarese, F., Poerio, A., Muratore, F., Ferrari, F., Mughetti, M., Franchini, L., Neziri, E., Miceli, M., Minguzzi, M. T., Mellini, L., Piciucchi, S., Gamberini, Lorenzo, Tonetti, Tommaso, Spadaro, Savino, Zani, Gianluca, Mazzoli, Carlo Alberto, Capozzi, Chiara, Giampalma, Emanuela, Bacchi Reggiani, Maria Letizia, Bertellini, Elisabetta, Castelli, Andrea, Cavalli, Irene, Colombo, Davide, Crimaldi, Federico, Damiani, Federica, Fogagnolo, Alberto, Fusari, Maurizio, Gamberini, Emiliano, Gordini, Giovanni, Laici, Cristiana, Lanza, Maria Concetta, Leo, Mirco, Marudi, Andrea, Nardi, Giuseppe, Ottaviani, Irene, Papa, Raffaella, Potalivo, Antonella, Russo, Emanuele, Taddei, Stefania, Volta, Carlo Alberto, and Ranieri, V Marco

Subjects
medicine.medical_specialty, ARDS, medicine.medical_treatment, artificial, Outcomes, Critical Care and Intensive Care Medicine, law.invention, NO, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, law, Coronavirus disease 2019, Intensive care, Outcomes, mortality, Respiration, artificial, medicine, 030212 general & internal medicine, Renal replacement therapy, business.industry, Research, Respiration, Organ dysfunction, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Intensive care unit, mortality, Respiratory failure, Emergency medicine, SOFA score, medicine.symptom, business
Abstract

Background A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. Methods This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Results Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Conclusions Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. Trial registration NCT04411459

Published
2020

3. Health-related quality of life profiles, trajectories, persistent symptoms and pulmonary function one year after ICU discharge in invasively ventilated COVID-19 patients, a prospective follow-up study

Author

Antonio Poerio, Andrea Castelli, Sara Piciucchi, Giulia Falò, Davide Allegri, Marco Verri, Andrea Marudi, Massimiliano Mazzolini, Michele Imbriani, Loredana Franchini, Carlo Coniglio, Mirco Leo, Antonella Potalivo, Luigi Lazzari Agli, Roberta Nicali, Marco Cavagnino, Guglielmo Consales, Marina Terzitta, Harri Sintonen, Raffaella Papa, Maria Teresa Minguzzi, Cristiana Laici, Paolo Orlandi, Federica Damiani, Carlo Alberto Mazzoli, Silvia Orlando, Vito Marco Ranieri, Iacopo Cappellini, Valentina Chiarini, Elisa Marinangeli, Stefano Oldani, Virginia Buldini, Marco Tartaglione, Gianluca Zani, Lorenzo Mellini, Carlo Alberto Volta, Irene Ottaviani, Silvia Candini, Filippo Becherucci, Emanuela Giampalma, Maria Concetta Lanza, Federica Ciccarese, Irene Cavalli, Annalisa Marchio, Bruno Balbi, Fabrizio Racca, Matteo Monari, Luca Morini, Anna Malfatto, Elisabetta Bertellini, Francesco Boni, Emanuele Russo, Lorenzo Viola, Michele Valli, Savino Spadaro, Martina Ferioli, Emanuele Matteo, Giovanni Gordini, Marco Contoli, Ilaria Valentini, Chiara Tartivita, Alessia Guzzo, Lorenzo Giuntoli, Gaetano Scaramuzzo, Davide Colombo, Jessica Maccieri, Luca Bissoni, Stefano Nava, Angela Bellocchio, Patrizio Goti, Laura Bernabé, Jonathan Montomoli, Stefano Maitan, Tommaso Meconi, Angelo Senzi, Lorenzo Gamberini, Silvia Pareschi, Stefania Taddei, Angelica Venni, Fabio Ferrari, Marco Miceli, Chiara Capozzi, Elisabetta Marangoni, Lorenzo Tutino, Giulia Felloni, Antonio Siniscalchi, Giacinto Pizzilli, Francesco Muratore, Giorgia Dalpiaz, Federico Moro, Daniele Fecarotti, Vanni Agnoletti, Gabriele Melegari, Rita Golfieri, Federico Domenico Baccarini, Francesca Facondini, Patrizia Pompa Cleta, Marianna Padovani, Eva Bernardi, Tommaso Tonetti, Angelina Adduci, Federico Daniele, Anna Filomena Ferravante, Maurizio Fusari, Igor Bacchilega, Claudia Ravaglia, Nicola Cilloni, Martina Mughetti, Vittorio Pavoni, Ersenad Neziri, Irene Prediletto, Aline Pagni, Gamberini L., Mazzoli C.A., Prediletto I., Sintonen H., Scaramuzzo G., Allegri D., Colombo D., Tonetti T., Zani G., Capozzi C., Dalpiaz G., Agnoletti V., Cappellini I., Melegari G., Damiani F., Fusari M., Gordini G., Laici C., Lanza M.C., Leo M., Marudi A., Papa R., Potalivo A., Montomoli J., Taddei S., Mazzolini M., Ferravante A.F., Nicali R., Ranieri V.M., Russo E., Volta C.A., Spadaro S., Tartaglione M., Chiarini V., Buldini V., Coniglio C., Moro F., Orlando S., Fecarotti D., Cilloni N., Giuntoli L., Bellocchio A., Matteo E., Pizzilli G., Siniscalchi A., Tartivita C., Cavalli I., Castelli A., Marchio A., Bacchilega I., Bernabe L., Facondini F., Morini L., Bissoni L., Viola L., Meconi T., Pavoni V., Venni A., Pagni A., Cleta P.P., Cavagnino M., Guzzo A., Malfatto A., Adduci A., Pareschi S., Bertellini E., Maccieri J., Marinangeli E., Racca F., Verri M., Falo G., Marangoni E., Ottaviani I., Boni F., Felloni G., Baccarini F.D., Terzitta M., Maitan S., Tutino L., Senzi A., Consales G., Becherucci F., Imbriani M., Orlandi P., Candini S., Golfieri R., Ciccarese F., Poerio A., Muratore F., Ferrari F., Mughetti M., Giampalma E., Franchini L., Neziri E., Miceli M., Minguzzi M.T., Mellini L., Piciucchi S., Monari M., Valli M., Daniele F., Ferioli M., Nava S., Lazzari Agli L.A., Valentini I., Bernardi E., Balbi B., Contoli M., Padovani M., Oldani S., Ravaglia C., and Goti P.

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Health-related quality of life, Population, Article, NO, Pulmonary function testing, 03 medical and health sciences, 0302 clinical medicine, Quality of life, DLCO, Acute respiratory distress syndrome, COVID-19, Dyspnea, Respiratory function tests, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Survivors, education, Aged, Mechanical ventilation, Health related quality of life, education.field_of_study, Respiratory Distress Syndrome, business.industry, Middle Aged, Respiration, Artificial, Patient Discharge, humanities, 3. Good health, Intensive Care Units, 030228 respiratory system, Italy, Quality of Life, Female, business, Icu discharge, Follow-Up Studies
Abstract

Background Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. Methods We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. Results We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. Conclusions HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. Trial registration NCT04411459.

Published
2021

4. Safety and Effectiveness of Carbon Dioxide Removal CO2RESET Device in Critically Ill Patients.

Author

Taccone FS, Rinaldi S, Annoni F, Nobile L, Di Nardo M, Maccieri J, Aliberti A, Malfertheiner MV, Marudi A, Broman LM, and Belliato M

Abstract

Background: In this retrospective study, we report the effectiveness and safety of a dedicated extracorporeal carbon dioxide removal (ECCO 2 R) device in critically ill patients., Methods: Adult patients on mechanical ventilation due to acute respiratory distress syndrome (ARDS) or decompensated chronic obstructive pulmonary disease (dCOPD), who were treated with a dedicated ECCO 2 R device (CO2RESET, Eurosets, Medolla, Italy) in case of hypercapnic acidemia, were included. Repeated measurements of CO 2 removal (VCO 2 ) at baseline and 1, 12, and 24 h after the initiation of therapy were recorded., Results: Over a three-year period, 11 patients received ECCO 2 R (median age 60 [43-72] years) 3 (2-39) days after ICU admission; nine patients had ARDS and two had dCOPD. Median baseline pH and PaCO 2 levels were 7.27 (7.12-7.33) and 65 (50-84) mmHg, respectively. With a median ECCO 2 R blood flow of 800 (500-800) mL/min and maximum gas flow of 6 (2-14) L/min, the VCO 2 at 12 h after ECCO 2 R initiation was 157 (58-183) mL/min. Tidal volume, respiratory rate, and driving pressure were significantly reduced over time. Few side effects were reported., Conclusions: In this study, a dedicated ECCO 2 R device provided a high VCO 2 with a favorable risk profile.

Published
2023
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5. Ceftazidime/Avibactam in Ventilator-Associated Pneumonia Due to Difficult-to-Treat Non-Fermenter Gram-Negative Bacteria in COVID-19 Patients: A Case Series and Review of the Literature.

Author

Burastero GJ, Orlando G, Santoro A, Menozzi M, Franceschini E, Bedini A, Cervo A, Faltoni M, Bacca E, Biagioni E, Coloretti I, Melegari G, Maccieri J, Busani S, Bertellini E, Girardis M, Ferrarini G, Rofrano L, Sarti M, Mussini C, and Meschiari M

Abstract

Ventilator-associated pneumonia (VAP) in critically ill patients with COVID-19 represents a very huge global threat due to a higher incidence rate compared to non-COVID-19 patients and almost 50% of the 30-day mortality rate. Pseudomonas aeruginosa was the first pathogen involved but uncommon non-fermenter gram-negative organisms such as Burkholderia cepacea and Stenotrophomonas maltophilia have emerged as other potential etiological causes. Against carbapenem-resistant gram-negative microorganisms, Ceftazidime/avibactam (CZA) is considered a first-line option, even more so in case of a ceftolozane/tazobactam resistance or shortage. The aim of this report was to describe our experience with CZA in a case series of COVID-19 patients hospitalized in the ICU with VAP due to difficult-to-treat (DTT) P. aeruginosa , Burkholderia cepacea , and Stenotrophomonas maltophilia and to compare it with data published in the literature. A total of 23 patients were treated from February 2020 to March 2022: 19/23 (82%) VAPs were caused by Pseudomonas spp. (16/19 DTT), 2 by Burkholderia cepacea , and 6 by Stenotrophomonas maltophilia ; 12/23 (52.1%) were polymicrobial. Septic shock was diagnosed in 65.2% of the patients and VAP occurred after a median of 29 days from ICU admission. CZA was prescribed as a combination regimen in 86% of the cases, with either fosfomycin or inhaled amikacin or cotrimoxazole. Microbiological eradication was achieved in 52.3% of the cases and the 30-day overall mortality rate was 14/23 (60.8%). Despite the high mortality of critically ill COVID-19 patients, CZA, especially in combination therapy, could represent a valid treatment option for VAP due to DTT non-fermenter gram-negative bacteria, including uncommon pathogens such as Burkholderia cepacea and Stenotrophomonas maltophilia .

Published
2022
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6. Cytokine mass balance levels in donation after circulatory death donors using hemoadsorption: Case series report.

Author

Baroni S, Marudi A, Rinaldi S, Ghedini S, Magistri P, Piero Guerrini G, Olivieri T, Dallai C, Talamonti M, Maccieri J, Benedetto FD, and Bertellini E

Subjects
Cytokines, Death, Graft Survival, Humans, Middle Aged, Perfusion, Tissue Donors, Kidney Transplantation, Tissue and Organ Procurement
Abstract

The use of hemadsorption has been purposed to reduce cytokine levels during the reperfusion phase during donation after circulatory death (DCD) programs. This paper aims to describe a cases series of the inflammatory cytokine levels before and after hemadsorption during normothermic reperfusion in DCD donors of liver and kidneys. In this observational pilot paper, we describe 8 DCD donors of liver or kidneys in our center from the year 2018 to 2019. All DCD donor subjects had similar age, were younger than 60 years, without evident critical conditions, no liver or kidney dysfunction known, and they presented with poor neurological outcomes instrumentally and clinically documented. We observed in our patients an interesting reduction of IL-10 and TNF-α levels during the normothermic reperfusion with hemadsorption. We transplanted all livers and kidneys from DCD donors without significant compliances.

Published
2022
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