Giacomo Grasselli1, Tommaso Tonetti2, Alessandro Protti3, Thomas Langer4, Massimo Girardis5, Giacomo Bellani6, John Laffey7, Gianpaolo Carrafiello8, Luca Carsana9, Chiara Rizzuto10, Alberto Zanella1, Vittorio Scaravilli11, Giacinto Pizzilli2, Domenico Luca Grieco12, Letizia Di Meglio13, Gennaro de Pascale12, Ezio Lanza14, Francesco Monteduro15, Maurizio Zompatori15, Claudia Filippini16, Franco Locatelli17, Maurizio Cecconi3, Roberto Fumagalli4, Stefano Nava18, Jean-Louis Vincent19, Massimo Antonelli20, Arthur S Slutsky21, Antonio Pesenti1, V Marco Ranieri22. 1. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 2. Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. 3. Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy. 4. Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy. 5. Department of Anesthesia and Intensive Care, University Hospital of Modena, Modena, Italy. 6. Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Department of Anesthesia and Intensive Care Medicine, ASST Monza-Ospedale San Gerardo, Monza, Italy. 7. Regenerative Medicine Institute at CÚRAM Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland; Anaesthesia and Intensive Care Medicine, School of Medicine, National University of Ireland Galway, Galway, Ireland. 8. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Dipartimento di Scienze della Salute, University of Milan, Milan, Italy. 9. Department of Anatomy and Histopathology, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy. 10. Department of Anesthesia and Intensive Care Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Polo Universitario, University of Milan, Milan, Italy. 11. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. 12. Department of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy. 13. Dipartimento di Scienze della Salute, University of Milan, Milan, Italy. 14. Humanitas Clinical and Research Center-IRCCS, Milan, Italy. 15. Dipartimento di Radiologia, Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. 16. Dipartimento di Scienze Chirurgiche, Università di Torino, Torino, Italy. 17. Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children Hospital, Rome, Italy. 18. Department of Clinical, Integrated and Experimental Medicine, Respiratory and Critical Care Unit, S Orsola-Malpighi Hospital, Alma Mater University, Bologna, Italy. 19. Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 20. Department of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. 21. Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, ON, Canada. 22. Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna, Bologna, Italy. Electronic address: m.ranieri@unibo.it.
Abstract
BACKGROUND: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. METHODS: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. FINDINGS: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). INTERPRETATION: Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates. FUNDING: None.
BACKGROUND:Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. METHODS: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. FINDINGS: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). INTERPRETATION:Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates. FUNDING: None.
Authors: Stefan Kluge; Uwe Janssens; Christoph D Spinner; Michael Pfeifer; Gernot Marx; Christian Karagiannidis Journal: Dtsch Arztebl Int Date: 2021-01-11 Impact factor: 5.594
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