Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients

Gaetano Perchiazzi, Aleksandra Larina, Tomas Hansen, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Mariangela Pellegrini, Gaetano Perchiazzi, Aleksandra Larina, Tomas Hansen, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Mariangela Pellegrini

Abstract

Background: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored.

Objective: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution.

Methods: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated.

Results: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04).

Conclusions: The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids.

Trial registration: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

Keywords: COVID-19; Dual-energy CT; Hypoxic pulmonary vasoconstriction; Steroids.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Dual-energy computed tomography (DECT) image acquisition and analysis. Left panel: DECT. A simplified representation of the DECT technique used, the SOMATOM Definition Flash, Siemens AG, Erlangen, Germany with two X-ray sources, characterized by two voltages (100 kVp and Sn 140 kVp), and two corresponding detectors rotating at a known constant angle. Central panel: Selected DECT scans. Coronal representation of a lung. Twenty DECT images, equally distributed between the apex and the diaphragmatic dome, were selected along the cranial–caudal axis. Both lungs were analyzed. Right panel: Images obtained by singo.via. Images used for further analysis. Representative example of pulmonary gas volume map and pulmonary blood volume map
Fig. 2
Fig. 2
Dual-energy computed tomography image analysis. Pulmonary gas volume maps were characterized by a HU range of − 1000 to + 100 HU. Pulmonary blood volume maps were characterized by a HU range of − 100 to + 150 HU. To assess hypoxic pulmonary vasoconstriction, pulmonary blood volume distribution was assessed for the whole lung and for the hypoinflated lung, the latter characterized by poorly inflated and non-inflated lung regions (HU between − 500 and + 100). A region of interest for hypoinflated lung (Hypoinflation ROI) was obtained extrapolating hypoinflated areas (Hypoinflation Map) from the pulmonary gas volume map. Hence, the hypoinflated ROI was applied to pulmonary blood volume map to analyze blood volume distribution of the hypoinflated areas
Fig. 3
Fig. 3
HU distribution for pulmonary gas volume map and blood volume maps, for the whole study population (n = 60 patients). Above: the HU distribution for pulmonary gas volume maps in the whole lung parenchyma; middle: HU distribution for pulmonary blood volume maps in the whole lung parenchyma; below: HU distribution for pulmonary blood volume maps in the hypoinflated lung parenchyma. x-axis: HU values. y-axis: percent of voxels compared to the total amount of voxels. Values represented as mean ± standard deviation (SD) or percent
Fig. 4
Fig. 4
HU distribution for pulmonary gas volume map and blood volume maps, separately for the No-Steroids group (n = 17 patients; Panel A) and the Steroids group (n = 43 patients; Panel B). Above: the HU distribution for pulmonary gas volume maps in the whole lung parenchyma; middle: HU distribution for pulmonary blood volume maps in the whole lung parenchyma; below: HU distribution for pulmonary blood volume maps in the hypoinflated lung parenchyma. x-axis: HU values. y-axis: percent of voxels compared to the total amount of voxels. Values represented as mean ± standard deviation (SD) or percent. *: for statistical differences between whole lung parenchyma (middle) and hypoinflated parenchyma (Below); †: for statistical differences between the No-Steroids group (Panel A) and the Steroids group (Panel B)
Fig. 5
Fig. 5
Representative example of DECT scans collected on the No-Steroids group (left) and the Steroids group (right). On the left: Patient not treated with steroids (No-Steroids group). On the right: Patient treated with steroids (Steroids group). For both No-Steroids and Steroids group, upper images show a pulmonary gas volume image (left) and the corresponding map (right); lower images show a pulmonary blood volume image (left) and the corresponding map (right). Different colormaps have been used to emphasize different degree of pulmonary gas and blood volume. For pulmonary gas volume maps, the range of HU is between − 1000 and + 100 HU. For pulmonary blood volume maps, the range of HU is between 0 and + 100 HU. 0 HU corresponding to non-perfused areas, 100 HU corresponding to highly perfused areas. The red arrow indicates the areas of preserved hypoxic pulmonary vasoconstriction where the areas of low pulmonary blood volume correspond to the areas of low inflation

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