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Communication

Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

by
Tommaso Tonetti
1,*,
Giacomo Grasselli
2,3,
Paola Rucci
4,
Francesco Alessandri
5,
Alessio Dell’Olio
1,
Annalisa Boscolo
6,
Laura Pasin
6,
Nicolò Sella
6,
Chiara Mega
1,
Rita Maria Melotti
1,
Massimo Girardis
7,
Stefano Busani
7,
Giacomo Bellani
8,9,
Giuseppe Foti
8,9,
Domenico Luca Grieco
10,
Vittorio Scaravilli
2,3,
Alessandro Protti
11,12,
Thomas Langer
8,13,
Luciana Mascia
4,
Francesco Pugliese
5,
Maurizio Cecconi
11,12,
Roberto Fumagalli
8,13,
Stefano Nava
14,
Massimo Antonelli
10,
Arthur S. Slutsky
15,
Paolo Navalesi
6,
Antonio Pesenti
2,3 and
Vito Marco Ranieri
1add Show full author list remove Hide full author list
1
Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Anesthesia and Intensive Care Medicine, IRCCS Policlinico di Sant’Orsola, Università di Bologna, 40138 Bologna, Italy
2
Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy
3
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
4
Dipartimento di Scienze Biomediche e Neuromotorie (DIBINEM), Alma Mater Studiorum Università di Bologna, 40126 Bologna, Italy
5
Department of Anaesthesia and Intensive Care, Sapienza University of Rome, 00161 Rome, Italy
6
Anesthesia and Critical Care, Department of Medicine-DIMED, University Hospital of Padua, 35127 Padua, Italy
7
Anesthesia and Critical Care, Policlinico di Modena, Università di Modena e Reggio Emilia, 41125 Modena, Italy
8
Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
9
Department of Anesthesia and Intensive Care Medicine, ASST Monza—Ospedale San Gerardo, 20900 Monza, Italy
10
Department of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
11
Department of Biomedical Sciences, Humanitas University, 20089 Pieve Emanuele, Italy
12
Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
13
Dipartimento di Anestesia e Rianimazione Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy
14
Respiratory and Critical Care Unit, Department of Clinical, Integrated and Experimental Medicine (DIMES), S. Orsola-Malpighi Hospital, Alma Mater University, 40138 Bologna, Italy
15
Keenan Research Centre for Biomedical Science, St Michael’s Hospital, Toronto, ON M5B 1W8, Canada
 
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*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(9), 1228; https://doi.org/10.3390/biomedicines9091228
Submission received: 16 August 2021 / Accepted: 9 September 2021 / Published: 15 September 2021
(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)
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Abstract

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.
Keywords: acute respiratory distress syndrome; COVID-19; D-dimer; static compliance; mechanical ventilation acute respiratory distress syndrome; COVID-19; D-dimer; static compliance; mechanical ventilation

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MDPI and ACS Style

Tonetti, T.; Grasselli, G.; Rucci, P.; Alessandri, F.; Dell’Olio, A.; Boscolo, A.; Pasin, L.; Sella, N.; Mega, C.; Melotti, R.M.; et al. Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study. Biomedicines 2021, 9, 1228. https://doi.org/10.3390/biomedicines9091228

AMA Style

Tonetti T, Grasselli G, Rucci P, Alessandri F, Dell’Olio A, Boscolo A, Pasin L, Sella N, Mega C, Melotti RM, et al. Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study. Biomedicines. 2021; 9(9):1228. https://doi.org/10.3390/biomedicines9091228

Chicago/Turabian Style

Tonetti, Tommaso, Giacomo Grasselli, Paola Rucci, Francesco Alessandri, Alessio Dell’Olio, Annalisa Boscolo, Laura Pasin, Nicolò Sella, Chiara Mega, Rita Maria Melotti, and et al. 2021. "Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study" Biomedicines 9, no. 9: 1228. https://doi.org/10.3390/biomedicines9091228

APA Style

Tonetti, T., Grasselli, G., Rucci, P., Alessandri, F., Dell’Olio, A., Boscolo, A., Pasin, L., Sella, N., Mega, C., Melotti, R. M., Girardis, M., Busani, S., Bellani, G., Foti, G., Grieco, D. L., Scaravilli, V., Protti, A., Langer, T., Mascia, L., ... Ranieri, V. M. (2021). Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study. Biomedicines, 9(9), 1228. https://doi.org/10.3390/biomedicines9091228

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