Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS

Abstract

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11–38) vs. 11 (6–26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0–5.2) versus 1.9 (1.0–5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = − 0.60; p = 0.001) and within-subjects correlation (r = − 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

Pulmonary Edema in COVID-19 Treated with Furosemide and Negative Fluid Balance (NEGBAL): A Different and Promising Approach

“…Furthermore, in the biomedical published literature, unfortunately, we did not find a similar approach for pulmonary edema in COVID-19. However, there are numerous reports of pulmonary edema [ 4 , 5 , 6 , 7 , 16 , 17 ] together with evidence of volume overload [ 26 , 27 , 28 , 29 ] in COVID-19. This evidence, added to the promising clinical response to NEGBAL, support this approach to pulmonary edema in COVID-19 as a biological plausibility.…”

“…The “first hit” of COVID-19 pneumonitis [ 49 ], followed by dysregulation RAAS [ 17 ] “second hit”, generating excess of intra- and extravascular fluid, causing volume overload [ 26 , 28 , 29 ] and pulmonary edema [ 4 , 5 , 6 , 7 ]. With unresolved edema, appeared a “third hit” characterized by infection, fibrosis, more inflammation, and ending in ARDS [ 47 , 50 ] (see Supplementary Materials: Figures S1–S6 ).…”

“…A posteriori, it ensues a dilatation of the superior vena cava, progressively, also the cardiac index [ 27 ] is added, and the cardiac axis is expanded, increasing the dilatation of the right ventricle [ 28 , 29 ]. This causes an increase of the hydrostatic pressure [ 25 , 30 ] and the consequent pulmonary edema [ 4 , 5 , 6 , 7 , 16 , 17 ]. Once the negative fluid balance approach was established, this harmful sequence was reverted.…”

“…In COVID-19, pulmonary edema is described [ 4 , 5 , 6 , 7 ]; however, the dominant paradigm is focused on cytokine storm [ 8 , 9 , 10 , 11 , 12 ] as responsible for lung injury and subsequent acute respiratory distress syndrome (ARDS) [ 5 , 13 ]. Not everyone agreed with this paradigm.…”

“…There are bibliographic mentions of pulmonary edema in COVID 19 [ 4 , 5 , 6 , 7 ], as well as evidence of volume overload in COVID-19: Lang et al describes frequent and pronounced vasculature in affected lung areas that may be suggestive of disordered vasoregulation [ 26 ]. Eslami et al observed increased cardiothoracic ratio [ 27 ] and it is also described as right ventricular dilatation [ 28 , 29 ].…”