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1. Long-term dyspnea, regional ventilation distribution and peripheral lung function in COVID-19 survivors: a 1 year follow up study

Author

Gaetano Scaramuzzo, Luca Ronzoni, Gianluca Campo, Paolo Priani, Chiara Arena, Riccardo La Rosa, Cecilia Turrini, Carlo Alberto Volta, Alberto Papi, Savino Spadaro, and Marco Contoli

Subjects
COVID-19, Post COVID-19, Electrical impedance tomography, Spirometry, Pulmonary function test, Dyspnea, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Dyspnea is common after COVID-19 pneumonia and can be characterized by a defective CO2 diffusion (DLCO) despite normal pulmonary function tests (PFT). Nevertheless, DLCO impairment tends to normalize at 1 year, with no dyspnea regression. The altered regional distribution of ventilation and a dysfunction of the peripheral lung may characterize dyspnea at 1 year after COVID-19 pneumonia. We aimed at assessing the pattern of airway resistance and inflammation and the regional ventilation inhomogeneity in COVID-19 pneumonia survivors at 12-months after hospital discharge. Methods We followed up at 1-year patients previously admitted to the respiratory units (intensive care or sub-intensive care unit) for COVID-19 acute respiratory failure at 1-year after hospital discharge. PFT (spirometry, DLCO), impulse oscillometry (IOS), measurements of the exhaled nitric oxide (FENO) and Electrical Impedance Tomography (EIT) were used to evaluate lung volumes, CO2 diffusion capacity, peripheral lung inflammation/resistances and the regional inhomogeneity of ventilation distribution. A full medical examination was conducted, and symptoms of new onset (not present before COVID-19) were recorded. Patients were therefore divided into two groups based on the presence/absence of dyspnea (defined as mMRC ≥1) compared to evaluate differences in the respiratory function derived parameters. Results Sixty-seven patients were admitted between October and December 2020. Of them, 42/67 (63%) patients were discharged alive and 33 were evaluated during the follow up. Their mean age was 64 ± 11 years and 24/33 (73%) were males. Their maximum respiratory support was in 7/33 (21%) oxygen, in 4/33 (12%) HFNC, in 14/33 (42%) NIV/CPAP and in 8/33 (24%) invasive mechanical ventilation. During the clinical examination, 15/33 (45%) reported dyspnea. When comparing the two groups, no significant differences were found in PFT, in the peripheral airway inflammation (FENO) or mechanical properties (IOS). However, EIT showed a significantly higher regional inhomogeneity in patients with dyspnea both during resting breathing (0.98[0.96–1] vs 1.1[1–1.1], p = 0.012) and during forced expiration (0.96[0.94–1] vs 1 [0.98–1.1], p = 0.045). Conclusions New onset dyspnea characterizes 45% of patients 1 year after COVID-19 pneumonia. In these patients, despite pulmonary function test may be normal, EIT shows a higher regional inhomogeneity both during quiet and forced breathing which may contribute to dyspnea. Clinical trial registration Clinicaltrials.gov NCT04343053, registration date 13/04/2020.

Published
2022
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2. Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

Author

Joachim Gerss, Javier Ripollés-Melchor, Emmanuel Futier, Melanie Meersch, Carola Wempe, Detlef Kindgen-Milles, Alexander Zarbock, Markus W Hollmann, Sigismond Lasocki, Thomas Rimmele, Tim Rahmel, Michael Adamzik, Hartmuth Nowak, Ingeborg Welters, Brian Johnston, Ane Abad-motos, Alfredo Abad-gurumeta, Marc Moritz Berger, Davide Ricci, Maurizio Cecconi, Gudrun Kunst, Christian Stoppe, Christian Putensen, Marlies Ostermann, Sascha Ott, Brijesh Patel, Gabriele Baldini, Antoine Lamblin, Karen Williams, Elena Mancini, Christian Arndt, Hinnerk Wulf, Marc Irqsusi, Wim Vandenberghe, John Kellum, Raphael Weiss, Jackie Donovan, Lui G Forni, Giacomo Monti, Céline Monard, Markus A Weigand, Thorsten Brenner, Ulrich Jaschinski, Carlos Lopez, Maxime Leger, Emmanuel Rineau, Philipp Simon, María Gómez-Rojo, Lars Bergmann, Alicia Waite, Savino Spadaro, Alexander Wolf, Andrew Spence, Simon Dubler, Alexander PJ Vlaar, Patrick Schober, Ben C Creagh-Brown, Nandor Marczin, Emilio Maseda, Christian Strauss, Stefano Romagnoli, Christian Nusshag, Ulrich Gobel, Ángel Candela-Toha, Jon Silversides, Nuttha Lumlertgul, Khaschayar Saadat-Gilani, Vincent Legros, Timo Brandenburger, Thomas Dimski, Laura Huthmann, Claude Pelletier, Manon Schleß, Peter Rosenberger, Helene Häberle, Jan Gerrit Haaker, Matthias Gründel, Lucia Cattin, Laura Villarino Villa, Juan Victor Lorente, Christine Martin, Jan Larmann, Wolfgang Bauer, Giovanni Borghi, Benjamin O’Brien, Thilo von Groote, Antoine Guillaume Schneider, Silvia De Rosa, Diego Parise, Alice Bernard, Paula Fernández-Valdes-Bango, Irene Romero Bhathal, A Suarez-de-la-Rica, Gianluca Villa, Raquel García-Álvarez, Antonio Siniscalchi, Richard Ellerkmann, Florian Espeter, Christian Porschen, Mahan Sadjadi, Michael Storck, Tobias Brix, Dana Meschede, Wida Amini, Carina Stenger, Julius Freytag, Jens Brands, Matthias Unterberg, Britta Marko, Fabian Dusse, Wolfgang A Wetsch, Sandra E Stoll, Hendrik Drinhaus, Bernd W Böttiger, Onnen Mörer, Lars-Olav Harnisch, Roswitha Lubjuhn, Daniel Heise, Christian Bode, Andrea Sauer, Konrad Peukert, Lennart Wild, Philippe Kruse, Jan Menzenbach, Valbona Mirakaj, Sabine Hermann, Stefanie Decker, Mona Jung-König, Tobias Hölle, Sarah Dehne, Jörg Reutershan, Thomas Prüfer, Stefan Pielmeier, Indra Wimmelmeier, Michaela Scholz, Andrea Paris, Isabel Christina Gallego Zapata, Holger Pohl, Nirmeen Fayed, Kai Dielmann, Evelyn Martin, Tilo Koch, Alexander Mück, Philipp Deetjen, Ngoc Bich Mehlmann, Peter M Spieth, Andreas Güldner, Axel Rand, Maximillian Ragaller, Martin Mirus, Rebecca Bockholt, Marc Herzog, Maren Kleine-Brüggeney, Ant Isabelle Cristiani, Marion Ohl, Monica Vieira Da Silva, Gilda Filipe de Castro Reblo, Matthias Hilty, Katharina Spanaus, Benedetta Mura, Eleonora Terreni, Francesco Magiotti, Lorenzo Turi, Cristiana Laici, Chiara Capozzi, Andrea Castelli, Massimiliano Greco, Antonio Messina, Gianluca Castellani, Romina Aceto, Vinicio Danzi, Alessandro Rigobello, Massimo De Cal, Monica Zanella, Gaetano Scaramuzzo, Riccardo La Rosa, Paolo Priani, Alberto Volta Carlo, Stefano Turi, Martina Baiardo Redaelli, Marilena Marmiere, Kittisak Weerapolchai, Shelley Lorah, Fabiola D’Amato, Aneta Bociek, Rosario Lim, Benjie Cendreda, Reynaldo Dela Cuesta, Eirini Kosifidou, Zoka Milan, Juliana Fernanda, Emma Clarey, Daveena Meeks, Nicholas J Lees, Marco Scaramuzzi, Orinta Kviatkovske, Adam Glass, Christine Turley, Charlotte Quinn, Syeda Haider, Adam Rossiter, Syed Nasser, Ned Gilbert-Kawai, Tatjana Besse-Hammer, Eric Hoste, Hannah Schaubroeck, Jan De Waele, Jenni Breel, Eline de Klerk, Harm-Jan de Grooth, Lothar Schwarte, Alexander Loer, Alicia Ruiz-Escobar, Diana Fernández-García, Nerea Gómez-Pérez, Pascual Crespo-Aliseda, Cristina Cerro-Zaballos, Cristina Fernández-Martín, Eduardo Martín-Montero, Alejandro Suarez de la Rica, Héctor Berges Gutiérrez, Maria del Pino Heredia Pérez, Maria de los Reyes Bellido Fernández, Liena Izquierdo López, Javier Valiente Lourtau, Ma Angeles Ferre Colomer, Ma Azucena Pajares Moncho, Maria Jesús Montero Hernández, Esther Pérez Sancho, Silvia Polo Matínez, Pedro Rivera Soria, Maider Puyada Jáuregui, Hugo Rivera Ramos, Marta Antelo Adrán, Ramón Adalia Bartolomé, Patricia Galán Menéndez, Laura Llinares Espin, Yuri Santiago Loaiza Aldean, Víctor MoralesAriza, Rosalía Navarro-Perez, Luis Santé-Serna, Pedro de la Calle-Elguezabal, Rubén Sánchez-Martín, Inés De Soto, Pau Vallhonrat Alcántara, Laura Perelló Cerdà, Gal·la Rouras Hurtado, Paula Rodriguez Nieto, John Narros Sicluna, Angel Molero Molinero, Juan Pablo Nocete, Elena Murcia Sánchez, Stanislas Abrard, Marie-Luce Parrouffe, Frank Bidar, Lucie Aupetitgendre, Ugo Schiff, Bertille Paquette, Gaëlle Sellier, Nathalie Borgnetta, Benjamin Brochet, Thierry Floch, Julien Coffinet, and Marion Leclercq-Rouget

Subjects
Medicine
Abstract

Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration number NCT04647396.

Published
2023
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3. Effect of the Pandemic Outbreak on ICU-Associated Infections and Antibiotic Prescription Trends in Non-COVID19 Acute Respiratory Failure Patients

Author

Enrico Bussolati, Rosario Cultrera, Alessandra Quaranta, Valentina Cricca, Elisabetta Marangoni, Riccardo La Rosa, Sara Bertacchini, Alessandra Bellonzi, Riccardo Ragazzi, Carlo Alberto Volta, Savino Spadaro, and Gaetano Scaramuzzo

Subjects
General Medicine, healthcare-associated infections, multidrug resistance, COVID-19, acute respiratory failure, mechanical ventilation, antimicrobial therapy, SARS-CoV-2 pandemic1
Abstract

Background: The COVID-19 pandemic had a relevant impact on the organization of intensive care units (ICU) and may have reduced the overall compliance with healthcare-associated infections (HAIs) prevention programs. Invasively ventilated patients are at high risk of ICU-associated infection, but there is little evidence regarding the impact of the pandemic on their occurrence in non-COVID-19 patients. Moreover, little is known of antibiotic prescription trends in the ICU during the first wave of the pandemic. The purpose of this investigation is to assess the incidence, characteristics, and risk factors for ICU-associated HAIs in a population of invasively ventilated patients affected by non-COVID-19 acute respiratory failure (ARF) admitted to the ICU in the first wave of the COVID-19 pandemic, and to evaluate the ICU antimicrobial prescription strategies. Moreover, we compared HAIs and antibiotic use to a cohort of ARF patients admitted to the ICU the year before the pandemic during the same period. Methods: this is a retrospective, single-centered cohort study conducted at S. Anna University Hospital (Ferrara, Italy). We enrolled patients admitted to the ICU for acute respiratory failure requiring invasive mechanical ventilation (MV) between February and April 2020 (intra-pandemic group, IP) and February and April 2019 (before the pandemic group, PP). We excluded patients admitted to the ICU for COVID-19 pneumonia. We recorded patients’ baseline characteristics, ICU-associated procedures and devices. Moreover, we evaluated antimicrobial therapy and classified it as prophylactic, empirical or target therapy, according to the evidence of infection at the time of prescription and to the presence of a positive culture sample. We compared the results of the two groups (PP and IP) to assess differences between the two years. Results: One hundred and twenty-eight patients were screened for inclusion and 83 patients were analyzed, 45 and 38 in the PP and I group, respectively. We found a comparable incidence of HAIs (62.2% vs. 65.8%, p = 0.74) and multidrug-resistant (MDR) isolations (44.4% vs. 36.8% p= 0.48) in the two groups. The year of ICU admission was not independently associated with an increased risk of developing HAIs (OR = 0.35, 95% CI 0.16–1.92, p = 0.55). The approach to antimicrobial therapy was characterized by a significant reduction in total antimicrobial use (21.4 ± 18.7 vs. 11.6 ± 9.4 days, p = 0.003), especially of target therapy, in the IP group. Conclusions: ICU admission for non-COVID-19 ARF during the first wave of the SARS-CoV-2 pandemic was not associated with an increased risk of ICU-associated HAIs. Nevertheless, ICU prescription of antimicrobial therapy changed and significantly decreased during the pandemic.

Published
2022
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