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

Tonetti, Tommaso; Grasselli, Giacomo; Rucci, Paola; Alessandri, Francesco; Dell’Olio, Alessio; Boscolo, Annalisa; Pasin, Laura; Sella, Nicolò; Mega, Chiara; Melotti, Rita Maria; Girardis, Massimo; Busani, Stefano; Bellani, Giacomo; Foti, Giuseppe; Grieco, Domenico Luca; Scaravilli, Vittorio; Protti, Alessandro; Langer, Thomas; Mascia, Luciana; Pugliese, Francesco; Cecconi, Maurizio; Fumagalli, Roberto; Nava, Stefano; Antonelli, Massimo; Slutsky, Arthur S.; Navalesi, Paolo; Pesenti, Antonio; Ranieri, Vito Marco

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, PaO(2)/FiO(2) 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/cmH(2)O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH(2)O (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.